subject:(Integrase)

1. Ferreira, Mafalda Carneiro da Rita Alves. Resistência aos inibidores da integrase no tratamento da infeção pelo VIH.

Degree: 2016, RCAAP

URL: https://www.rcaap.pt/detail.jsp?id=oai:comum.rcaap.pt:10400.26/17592

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Dissertação para obtenção do grau de Mestre no Instituto Superior de Ciências da Saúde Egas Moniz

Objetivo: Avaliar a resistência aos inibidores da integrase (InSTIs)… (more)

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Dissertação para obtenção do grau de Mestre no Instituto Superior de Ciências da Saúde Egas Moniz

Objetivo: Avaliar a resistência aos inibidores da integrase (InSTIs) no tratamento de indivíduos infetados por VIH-1 e sob falência virológica na presença destes fármacos. Material e Métodos: Foram analisadas, retrospetivamente, isolados virais (região da integrase) pertencentes a 367 indivíduos, dos quais 213 (58%) homens e 154 (42%) mulheres, com idades compreendidas entre os 7 e os 83 anos. As mutações estudadas foram as descritas pela International Aids Society (IAS) como associadas a resistência aos InSTIs. Resultados: A frequência das mutações de resistência encontrada foi bastante variável, sendo a N155H a mutação com maior frequência e a mutação 121Y não foi encontrada. 33% (n=121) dos indivíduos estavam infetados por vírus do subtipo G, 26% (n=94) pelo subtipo B, 11% (n=39) pelo subtipo C, 10% (n=38) pelo subtipo CRF02_AG e os restantes 20% correspondem a outros subtipos. Foi ainda possível identificar a frequência com que as mutações ocorrem isoladamente e em associação, prevalecendo a presença de uma única mutação em 40% (n=33), embora 60% (n=48) dos doentes resistentes apresentem duas ou mais mutações. As mutações são globalmente independentes do subtipo (p≥0,05). No entanto, as mutações da posição 140 e 148 são exceção (p=0,011 e p=0,002, respetivamente) tendo uma maior prevalência no subtipo B. Verificou-se ainda, que a resistência aos InSTIs encontrada no sexo masculino (n=48) foi semelhante à encontrada no sexo feminino (n=33), 24% e 21%, respetivamente. As mutações da região do gene da integrase são independentes das outras classes terapêuticas (NRTIs, NNRTIs, IPs) que constituem o regime terapêutico, p=0,295. Conclusão: Neste estudo, 78% dos indivíduos apresentam suscetibilidade aos InSTIs, e os restantes 22% apresentaram mutações associadas a resistência no gene da integrase, que influenciam a resposta à terapêutica com InSTIs. Nesta população, a baixa utilização de regimes terapêuticos com EVG, teve como consequência a baixa prevalência das mutações T66I e S147G, E92Q, Q148, assim como a associação Q148 com a G140. A elevada prevalência das mutações N155H e T97A reflete a utilização do raltegravir. A reduzida presença das mutações Q148HRK e R263K favorece a possibilidade de tratamento sequencial com DTG.

Advisors/Committee Members: Gomes, Perpétua.

Subjects/Keywords: VIH; Integrase; Inibidores da integrase; Mutação; Resistência

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APA (6^th Edition):

Ferreira, M. C. d. R. A. (2016). Resistência aos inibidores da integrase no tratamento da infeção pelo VIH. (Thesis). RCAAP. Retrieved from https://www.rcaap.pt/detail.jsp?id=oai:comum.rcaap.pt:10400.26/17592

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Ferreira, Mafalda Carneiro da Rita Alves. “Resistência aos inibidores da integrase no tratamento da infeção pelo VIH.” 2016. Thesis, RCAAP. Accessed January 20, 2021. https://www.rcaap.pt/detail.jsp?id=oai:comum.rcaap.pt:10400.26/17592.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Ferreira, Mafalda Carneiro da Rita Alves. “Resistência aos inibidores da integrase no tratamento da infeção pelo VIH.” 2016. Web. 20 Jan 2021.

Vancouver:

Ferreira MCdRA. Resistência aos inibidores da integrase no tratamento da infeção pelo VIH. [Internet] [Thesis]. RCAAP; 2016. [cited 2021 Jan 20]. Available from: https://www.rcaap.pt/detail.jsp?id=oai:comum.rcaap.pt:10400.26/17592.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Ferreira MCdRA. Resistência aos inibidores da integrase no tratamento da infeção pelo VIH. [Thesis]. RCAAP; 2016. Available from: https://www.rcaap.pt/detail.jsp?id=oai:comum.rcaap.pt:10400.26/17592

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Manitoba

2. Parvez, Md. Kamal Uddin. Identification and characterization of new cellular interacting proteins of HIV-1 integrase.

Degree: Medical Microbiology, 2011, University of Manitoba

URL: http://hdl.handle.net/1993/4525

► HIV-1 integrase (IN) enzyme employs several viral and cellular proteins for nuclear translocation and crucial integration of viral cDNA. Successful identification of new viral/cellular interactions… (more)

Subjects/Keywords: HIV-1; Integrase

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Parvez, M. K. U. (2011). Identification and characterization of new cellular interacting proteins of HIV-1 integrase. (Masters Thesis). University of Manitoba. Retrieved from http://hdl.handle.net/1993/4525

Chicago Manual of Style (16^th Edition):

Parvez, Md Kamal Uddin. “Identification and characterization of new cellular interacting proteins of HIV-1 integrase.” 2011. Masters Thesis, University of Manitoba. Accessed January 20, 2021. http://hdl.handle.net/1993/4525.

MLA Handbook (7^th Edition):

Parvez, Md Kamal Uddin. “Identification and characterization of new cellular interacting proteins of HIV-1 integrase.” 2011. Web. 20 Jan 2021.

Vancouver:

Parvez MKU. Identification and characterization of new cellular interacting proteins of HIV-1 integrase. [Internet] [Masters thesis]. University of Manitoba; 2011. [cited 2021 Jan 20]. Available from: http://hdl.handle.net/1993/4525.

Council of Science Editors:

Parvez MKU. Identification and characterization of new cellular interacting proteins of HIV-1 integrase. [Masters Thesis]. University of Manitoba; 2011. Available from: http://hdl.handle.net/1993/4525

University of Southern California

3. Sanchez, Tino Wilson. Discovery of new HIV-1 integrase inhibitors.

Degree: MS, Pharmacy / Pharmaceutical Sciences, 2007, University of Southern California

URL: http://digitallibrary.usc.edu/cdm/compoundobject/collection/p15799coll127/id/484210/rec/2028

► We identified 49 novel HIV-1 IN inhibitors with a wide inhibitory profile. Furan and sulfonamide based inhibitors were tested in vitro against HIV-1 IN. Their… (more)

Subjects/Keywords: integrase; HIV

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APA (6^th Edition):

Sanchez, T. W. (2007). Discovery of new HIV-1 integrase inhibitors. (Masters Thesis). University of Southern California. Retrieved from http://digitallibrary.usc.edu/cdm/compoundobject/collection/p15799coll127/id/484210/rec/2028

Chicago Manual of Style (16^th Edition):

Sanchez, Tino Wilson. “Discovery of new HIV-1 integrase inhibitors.” 2007. Masters Thesis, University of Southern California. Accessed January 20, 2021. http://digitallibrary.usc.edu/cdm/compoundobject/collection/p15799coll127/id/484210/rec/2028.

MLA Handbook (7^th Edition):

Sanchez, Tino Wilson. “Discovery of new HIV-1 integrase inhibitors.” 2007. Web. 20 Jan 2021.

Vancouver:

Sanchez TW. Discovery of new HIV-1 integrase inhibitors. [Internet] [Masters thesis]. University of Southern California; 2007. [cited 2021 Jan 20]. Available from: http://digitallibrary.usc.edu/cdm/compoundobject/collection/p15799coll127/id/484210/rec/2028.

Council of Science Editors:

Sanchez TW. Discovery of new HIV-1 integrase inhibitors. [Masters Thesis]. University of Southern California; 2007. Available from: http://digitallibrary.usc.edu/cdm/compoundobject/collection/p15799coll127/id/484210/rec/2028

University of Southern California

4. Al Safi, Rasha. HIV-1 integrase and human APE1: two DNA-processing enzymes and two druggable targets.

Degree: MS, Pharmaceutical Sciences, 2011, University of Southern California

URL: http://digitallibrary.usc.edu/cdm/compoundobject/collection/p15799coll127/id/427286/rec/3202

► HIV-1 Integrase (IN) and the human apurinic/apyrimidinic endonuclease 1 (APE1) are two DNA-processing enzymes implicated in disease. IN catalyses the insertion of viral DNA into… (more)

Subjects/Keywords: HIV-1; integrase; APE1; cancer

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Al Safi, R. (2011). HIV-1 integrase and human APE1: two DNA-processing enzymes and two druggable targets. (Masters Thesis). University of Southern California. Retrieved from http://digitallibrary.usc.edu/cdm/compoundobject/collection/p15799coll127/id/427286/rec/3202

Chicago Manual of Style (16^th Edition):

Al Safi, Rasha. “HIV-1 integrase and human APE1: two DNA-processing enzymes and two druggable targets.” 2011. Masters Thesis, University of Southern California. Accessed January 20, 2021. http://digitallibrary.usc.edu/cdm/compoundobject/collection/p15799coll127/id/427286/rec/3202.

MLA Handbook (7^th Edition):

Al Safi, Rasha. “HIV-1 integrase and human APE1: two DNA-processing enzymes and two druggable targets.” 2011. Web. 20 Jan 2021.

Vancouver:

Al Safi R. HIV-1 integrase and human APE1: two DNA-processing enzymes and two druggable targets. [Internet] [Masters thesis]. University of Southern California; 2011. [cited 2021 Jan 20]. Available from: http://digitallibrary.usc.edu/cdm/compoundobject/collection/p15799coll127/id/427286/rec/3202.

Council of Science Editors:

Al Safi R. HIV-1 integrase and human APE1: two DNA-processing enzymes and two druggable targets. [Masters Thesis]. University of Southern California; 2011. Available from: http://digitallibrary.usc.edu/cdm/compoundobject/collection/p15799coll127/id/427286/rec/3202

Wayne State University

5. Ross, Kyla Nicole. Hiv Integrase Mechanisms Of Resistance To Raltegravir, Elvitegravir, And Dolutegravir.

Degree: MS, Biochemistry and Molecular Biology, 2015, Wayne State University

URL: https://digitalcommons.wayne.edu/oa_theses/458

► ABSTRACT HIV INTEGRASE MECHANISMS OF RESISTANCE TO RALTEGRAVIR, ELVITEGRAVIR, AND DOLUTEGRAVIR by KYLA ROSS December 2015 Advisor: Dr. Ladislau Kovari Major: Biochemistry and Molecular… (more)

▼ ABSTRACT HIV INTEGRASE MECHANISMS OF RESISTANCE TO RALTEGRAVIR, ELVITEGRAVIR, AND DOLUTEGRAVIR by KYLA ROSS December 2015 Advisor: Dr. Ladislau Kovari Major: Biochemistry and Molecular Biology Degree: Master of Science HIV-1 integrase (HIV-1 IN or IN) is a multimeric enzyme that integrates the HIV-1 genome into the chromosomes of infected CD4+ T-cells. Currently there are three FDA approved HIV-1 IN strand transfer inhibitors (INSTIs) used in clinical practice: raltegravir (RAL), elvitegravir (ELV), and dolutegravir (DTG). The [Q148H], [Q148H, G140S], [Q148R], [Q148R, G140A] and [N155H, E92Q] mutations decrease IN susceptibility to RAL and ELV and may result in therapeutic failure. As an indicator of protein flexibility, the root mean square deviation (RMSD) of each HIV-1 IN residue in the last 5 ns of a 40 ns molecular dynamics simulation was calculated for HIV-1 IN catalytic core domain as an apoprotein and in complex with RAL, ELV, and DTG to study how the mutations affect HIV-1 IN flexibility. In addition, we studied the relationship between HIV-1 IN flexibility and resistance. We found that the mutants reduced overall HIV-1 IN flexibility relative to the WT IN apoprotein. We also observed that the catalytic 140s loop in the HIV-1 IN-INSTI complexes were more flexible in mutants that displayed higher reported EC50 FC (fold change) values. To further investigate the mutations effect on the more complexed full length HIV-1 IN structure, we used molecular dynamics simulations to study the impact of the mutants on binary (IN-viral DNA complex) and ternary (IN-viral DNA- INSTI) IN flexibility. RMSD analyses revealed that that the mutants have a rigid structure relative to the WT IN. Furthermore, mutant IN showed transient changes in the secondary structure of the 140s loop compared to the WT. In addition to these reduced flexibility and structural changes, resistance mutations alter the binding mode of RAL, ELV, and DTG to IN and viral DNA. This study is the first to identify a structural basis of IN mechanism of resistance to INSTIs that develops under treatment pressure in HIV-1 IN. Advisors/Committee Members: Dr. Ladislau Kovari.

Subjects/Keywords: HIV-1; HIV-1 Integrase Resistance Mutations; Integrase Resistance; Integrase Strand Transfer Inhibitors; Protein Flexibility; Biochemistry; Bioinformatics; Virology

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Ross, K. N. (2015). Hiv Integrase Mechanisms Of Resistance To Raltegravir, Elvitegravir, And Dolutegravir. (Masters Thesis). Wayne State University. Retrieved from https://digitalcommons.wayne.edu/oa_theses/458

Chicago Manual of Style (16^th Edition):

Ross, Kyla Nicole. “Hiv Integrase Mechanisms Of Resistance To Raltegravir, Elvitegravir, And Dolutegravir.” 2015. Masters Thesis, Wayne State University. Accessed January 20, 2021. https://digitalcommons.wayne.edu/oa_theses/458.

MLA Handbook (7^th Edition):

Ross, Kyla Nicole. “Hiv Integrase Mechanisms Of Resistance To Raltegravir, Elvitegravir, And Dolutegravir.” 2015. Web. 20 Jan 2021.

Vancouver:

Ross KN. Hiv Integrase Mechanisms Of Resistance To Raltegravir, Elvitegravir, And Dolutegravir. [Internet] [Masters thesis]. Wayne State University; 2015. [cited 2021 Jan 20]. Available from: https://digitalcommons.wayne.edu/oa_theses/458.

Council of Science Editors:

Ross KN. Hiv Integrase Mechanisms Of Resistance To Raltegravir, Elvitegravir, And Dolutegravir. [Masters Thesis]. Wayne State University; 2015. Available from: https://digitalcommons.wayne.edu/oa_theses/458

The Ohio State University

6. Patel, Pratiq A. Functionalization of Nitrogen-Containing Heterocycles in the Synthesis of Biologically Active Molecules.

Degree: PhD, Chemistry, 2013, The Ohio State University

URL: http://rave.ohiolink.edu/etdc/view?acc_num=osu1382064973

► Nitrogen-containing heterocycles are commonly seen both in the pharmacophores of drug molecules and also in the cores of natural products. This dissertation explores the… (more)

▼ Nitrogen-containing heterocycles are commonly seen both in the pharmacophores of drug molecules and also in the cores of natural products. This dissertation explores the functionalization of nitrogen-containing heteroaromatic rings to access the highly substituted scaffolds of bioactive molecules within two distinct projects. Part I features medicinal chemistry efforts in the synthesis and derivatization of functionalized quinolines, indoles, pyridines, and pyrroles as novel HIV allosteric integrase inhibitors. Alternatively, part II involves synthetic efforts towards the indole subunit of the bioactive natural product, sespendole. HIV integrase (IN) plays a crucial role in the replication of the HIV virus as it catalyzes the transfer of the viral genetic code into the host genome. Raltegravir (Merck & Co) is the first FDA drug targeting this strand transfer catalytic activity; however, rapid viral mutation has since led to drug-resistance and a renewed interest in developing new integrase inhibitors. In this regard, the host enzyme lens-epithelium derived growth factor (LEDGF)-integrase interaction served as new targets for generating novel integrase inhibitors. Recently, independent studies by other groups resulted in the identification of 2-(quinolin-3-yl)acetic acid derivatives as allosteric integrase inhibitors (ALLINIs). Development of synthetic routes to these inhibitors and a series of structural analogues have facilitated elucidation of the novel multifunctional mechanism of action for this class of compounds. Additionally, the design of novel scaffolds as ALLINIs was investigated through a scaffold hopping technique, the derivatization of leads from an in silico screen, and a fragment-based drug design approach. These drug discovery methods have resulted in the syntheses of a structurally diverse class of compounds that have provided an insight on the structural and functional requirements of the binding pocket. Sespendole, an indolosesquiterpene alkaloid isolated from the fungus Pseudobotrytis terrestris FKA-25, was reported as a potent inhibitor of lipid droplet synthesis. The proposed biosynthesis of sespendole, which involves a carbocation induced cyclization/rearrangement cascade, initially intrigued our group and spurred our interest in the synthesis of this complex molecule. This dissertation focuses on the synthesis of the highly substituted indole subunit of sespendole. Direct functionalization of the indole nucleus at the C4 and C5 positions via application of Bartoli's Grignard addition and halogen-metal exchange chemistry resulted in the successful synthesis of the fully substituted indole subunit of sespendole. Advisors/Committee Members: Fuchs, James (Advisor), Forsyth, Craig (Committee Co-Chair).

Subjects/Keywords: Organic Chemistry; Chemistry; nitrogen-containing heterocycles; indole functionalization; HIV integrase; allosteric integrase inhibitors; integrase multimerization; sespendole; Bartoli Grignard addition

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Patel, P. A. (2013). Functionalization of Nitrogen-Containing Heterocycles in the Synthesis of Biologically Active Molecules. (Doctoral Dissertation). The Ohio State University. Retrieved from http://rave.ohiolink.edu/etdc/view?acc_num=osu1382064973

Chicago Manual of Style (16^th Edition):

Patel, Pratiq A. “Functionalization of Nitrogen-Containing Heterocycles in the Synthesis of Biologically Active Molecules.” 2013. Doctoral Dissertation, The Ohio State University. Accessed January 20, 2021. http://rave.ohiolink.edu/etdc/view?acc_num=osu1382064973.

MLA Handbook (7^th Edition):

Patel, Pratiq A. “Functionalization of Nitrogen-Containing Heterocycles in the Synthesis of Biologically Active Molecules.” 2013. Web. 20 Jan 2021.

Vancouver:

Patel PA. Functionalization of Nitrogen-Containing Heterocycles in the Synthesis of Biologically Active Molecules. [Internet] [Doctoral dissertation]. The Ohio State University; 2013. [cited 2021 Jan 20]. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=osu1382064973.

Council of Science Editors:

Patel PA. Functionalization of Nitrogen-Containing Heterocycles in the Synthesis of Biologically Active Molecules. [Doctoral Dissertation]. The Ohio State University; 2013. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=osu1382064973

7. Ni, Xiaoju. The study of susceptibility and resistance of HIV integrases to integrase strand transfer inhibitors and the development of novel single domain antibody targeting HIV integrase : La détermination de la susceptibilité et de la résistance des intégrases (INs) du virus de l’immunodéficience humaine aux inhibiteurs de transfert de brins de l'IN et le développement d’anticorps simple-chaîne ciblant l’IN.

Degree: Docteur es, Sciences de la vie et de la santé, 2011, Cachan, Ecole normale supérieure

URL: http://www.theses.fr/2011DENS0037

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Ce mémoire de thèse présente mes travaux sur la détermination de la susceptibilité et de la résistance des intégrases (INs) du virus de l’immunodéficience humaine… (more)

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Ce mémoire de thèse présente mes travaux sur la détermination de la susceptibilité et de la résistance des intégrases (INs) du virus de l’immunodéficience humaine (VIH) aux inhibiteurs de transfert de brins de l'IN (INSTIs) ainsi que le développement de fragments d’anticorps simple-chaîne (sdAbs) ciblant l’IN du VIH. Tout d’abord, car les études antérieures ont suggéré que les variations significatives de l’IN de souche CRF02_AG pourrait avoir des effets consécutifs sur l'interaction entre l'inhibiteur et l’IN, la susceptibilité de l’IN de souche CRF02_AG du VIH-1 aux dernières INSTIs a été déterminée. Accord avec l'étude in silico, nous avons mis en évidence que l’activité de 3’-processing et de transfert de brin des INs de souche B et de souche CRF02_AG sont comparables. La susceptibilité des INs recombinantes de souche CRF02_AG aux INSTIs utilisés (Raltégravir-RAL, Elevitégravir-EVG et L-731, 988) est similaire à celle de l’IN de souche B, malgré les variations naturelles qui se produisent dans les INs de souche CRF02_AG. Le polymorphisme de l’IN de CRF02_AG n’a pas d’effet significatif sur la susceptibilité aux INSTIs. Dans un second temps, la résistance de l’IN du VIH-2 au RAL, l’unique INSTI approuvé, a été confirmée in vitro avec des enzymes mutées portant des mutations de résistance. Les mutations aux positions 155 et 148 jouent un rôle similaire pour les VIH-1 et VIH-2, en rendant l'IN résistante au RAL. La mutation G140S confère peu de résistance, mais compense le défaut catalytique dû à la mutation Q148R. À l'inverse, Y143C seule ne confère pas de résistance au RAL excepté si la mutation E92Q est également présente. De plus, l'introduction de la mutation Y143C dans le mutant résistant N155H baisse le niveau de résistance de l’enzyme contenant la mutation N155H, ce qui pourrait expliquer l'absence de détection de ces deux mutations ensemble dans un seul génome. Enfin, des anti-VIH sdAbs avec nombreuses propriétés intéressantes ont été sélectionnés pour développer des agents antirétroviraux. Après la sélection de sdAb ciblant l’IN du VIH, nous avons obtenu des qui sdAbs qui reconnaissent spécifiquement une vaste gamme d’INs in vitro, y compris le mutant G140S/Q148R résistant aux INSTIs. Néanmoins, l'activité inhibitrice des sdAbs n'a pas été observée. Les sdAbs ciblant l’IN du VIH peuvent être utilisés pour d'autres applications, telles que des réactifs ciblant des nanocapteurs. À l'avenir, en raison des avantages uniques des sdAbs, le développement de sdAbs anti-IN du VIH qui bloquent la réplication du VIH reste attractive pour l'obtenir des inhibiteurs efficaces de l’IN.

This thesis presents the determination of susceptibility and resistance of HIV integrases (INs) to IN strand transfer inhibitors (INSTIs) and the development of single domain antibody (sdAb) targeting HIV IN. Firstly, the susceptibility of HIV-1 subtype CRF02_AG INs to the latest INSTIs was determined, since previous studies suggested that the significant variations of CRF02_AG IN may have consequential effects on the interaction…

Advisors/Committee Members: Mouscadet, Jean-François (thesis director).

Subjects/Keywords: VIH; Intégrase; Résistance; HIV; Integrase; Resistance

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Ni, X. (2011). The study of susceptibility and resistance of HIV integrases to integrase strand transfer inhibitors and the development of novel single domain antibody targeting HIV integrase : La détermination de la susceptibilité et de la résistance des intégrases (INs) du virus de l’immunodéficience humaine aux inhibiteurs de transfert de brins de l'IN et le développement d’anticorps simple-chaîne ciblant l’IN. (Doctoral Dissertation). Cachan, Ecole normale supérieure. Retrieved from http://www.theses.fr/2011DENS0037

Chicago Manual of Style (16^th Edition):

Ni, Xiaoju. “The study of susceptibility and resistance of HIV integrases to integrase strand transfer inhibitors and the development of novel single domain antibody targeting HIV integrase : La détermination de la susceptibilité et de la résistance des intégrases (INs) du virus de l’immunodéficience humaine aux inhibiteurs de transfert de brins de l'IN et le développement d’anticorps simple-chaîne ciblant l’IN.” 2011. Doctoral Dissertation, Cachan, Ecole normale supérieure. Accessed January 20, 2021. http://www.theses.fr/2011DENS0037.

MLA Handbook (7^th Edition):

Ni, Xiaoju. “The study of susceptibility and resistance of HIV integrases to integrase strand transfer inhibitors and the development of novel single domain antibody targeting HIV integrase : La détermination de la susceptibilité et de la résistance des intégrases (INs) du virus de l’immunodéficience humaine aux inhibiteurs de transfert de brins de l'IN et le développement d’anticorps simple-chaîne ciblant l’IN.” 2011. Web. 20 Jan 2021.

Vancouver:

Ni X. The study of susceptibility and resistance of HIV integrases to integrase strand transfer inhibitors and the development of novel single domain antibody targeting HIV integrase : La détermination de la susceptibilité et de la résistance des intégrases (INs) du virus de l’immunodéficience humaine aux inhibiteurs de transfert de brins de l'IN et le développement d’anticorps simple-chaîne ciblant l’IN. [Internet] [Doctoral dissertation]. Cachan, Ecole normale supérieure; 2011. [cited 2021 Jan 20]. Available from: http://www.theses.fr/2011DENS0037.

Council of Science Editors:

Ni X. The study of susceptibility and resistance of HIV integrases to integrase strand transfer inhibitors and the development of novel single domain antibody targeting HIV integrase : La détermination de la susceptibilité et de la résistance des intégrases (INs) du virus de l’immunodéficience humaine aux inhibiteurs de transfert de brins de l'IN et le développement d’anticorps simple-chaîne ciblant l’IN. [Doctoral Dissertation]. Cachan, Ecole normale supérieure; 2011. Available from: http://www.theses.fr/2011DENS0037

8. Arora, Rohit. Molecular mechanism of HIV-1 integrase inhibition by Raltegravir proposed by using of molecular modeling approaches : Mécanisme moléculaire de l'inhibition de l'intégrase du VIH-1 par le raltégravir proposé par l'utilisation d'approches de modélisation moléculaire.

Degree: Docteur es, Sciences de la vie et de la santé, 2012, Cachan, Ecole normale supérieure

URL: http://www.theses.fr/2012DENS0055

► L'intégrase (IN) rétrovirale est responsable de l’intégration de l'ADN viral du VIH-1dans l’ADN cellulaire, processus indispensable à la réplication virale. Ce processus se déroule en… (more)

▼ L'intégrase (IN) rétrovirale est responsable de l’intégration de l'ADN viral du VIH-1dans l’ADN cellulaire, processus indispensable à la réplication virale. Ce processus se déroule en deux étapes indépendantes, le 3’-processing et le transfert de brins, catalysées par l’IN. La compréhension des interactions entre l’IN et l’ADN viral et de la cinétique de formation des complexes pré-intégratifs a permis l’identification du raltégravir (RAL) et de l’elvitégravir (ELV) qui se sont avérés être des inhibiteurs très efficaces de la réplication virale. Le RAL, auparavant désigné sous le code MK-0518, est un nouveau médicament anti-VIH qui a obtenu son autorisation de commercialisation aux Etats-Unis sous le nom de IsentressTM le 12 octobre 2007. Le ELV est toujours en essais cliniques. Toutefois, comme on l'observe pour d'autres antirétroviraux, ces composés n’échappent cependant pas aux phénomènes de résistance. Des mutations de résistance spécifiques au RAL ont ainsi été identifiées chez des patients. À ce jour, aucune donnée expérimentale caractérisant la structure de l’IN du VIH-1, la structure au RAL et/ou les interactions du RAL avec sa cible n'a été rapporté.Premièrement, nous avons caractérisé les propriétés structurales et conformationnelles du RAL dans des états différents, en phase gazeuse, en solution dans l'eau et à l'état solide. Une etude détaillée a permis de caracteriser la reconnaissance du RAL par des cibles virals, l’IN et l’ADN viral avant et après la réaction de 3’-processing. Nous avons trouvé que le RAL adopte un large spectre de conformations et configurations dans des états isolés et/ou liés avec le(s) cible(s). Les meilleures score et poses de docking confirment que le modèle représentant le complexe IN•vADN est la cible biologiquement pertinente du RAL. Ce résultat est cohérent avec le mécanisme d'inhibition du RAL communément admise. Nous avons suggéré que le processus d'inhibition peut comprendre dans un premier temps la reconnaissance du RAL par l'ADN viral clivé et lié à un état intermédiaire de l’IN. Le RAL couplé à l’ADN viral montre une orientation à l'extérieur de tous les atomes d'oxygène, d'excellents agents putatifs pour capturer de cations Mg2+, ce qui pourrait faciliter l'insertion du RAL dans le site actif. La flexibilité conformationnelle du RAL permet l'adaptation de l'inhibiteur dans une poche relativement grande de du complexe IN•vADN, permettant la production de diverses conformations du RAL. Nous croyons que cette diversité des conformations du RAL contribue à la reconnaissance de résidus enzymatiques et peut influer sur le choix des voies alternatives de résistance au RAL observées cliniquement.Nous avons étudié également la reconnaissance par l’IN des inhibiteurs du VIH appartenant à différents souches, B et CRF02_AG. Nous avons montré que la structure de l’IN des deux souches est quasi-identique. Le docking du RAL et de deux autres inhibiteurs de transfert de brins (ELV et L731_988) sur chaque modèle montre que leur reconnaissance par deux différentes souches cibles est… Advisors/Committee Members: Tchertanov, Luba (thesis director).

Subjects/Keywords: VIH; Intégrase; Résitance; HIV; Integrase; Resistance

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Arora, R. (2012). Molecular mechanism of HIV-1 integrase inhibition by Raltegravir proposed by using of molecular modeling approaches : Mécanisme moléculaire de l'inhibition de l'intégrase du VIH-1 par le raltégravir proposé par l'utilisation d'approches de modélisation moléculaire. (Doctoral Dissertation). Cachan, Ecole normale supérieure. Retrieved from http://www.theses.fr/2012DENS0055

Chicago Manual of Style (16^th Edition):

Arora, Rohit. “Molecular mechanism of HIV-1 integrase inhibition by Raltegravir proposed by using of molecular modeling approaches : Mécanisme moléculaire de l'inhibition de l'intégrase du VIH-1 par le raltégravir proposé par l'utilisation d'approches de modélisation moléculaire.” 2012. Doctoral Dissertation, Cachan, Ecole normale supérieure. Accessed January 20, 2021. http://www.theses.fr/2012DENS0055.

MLA Handbook (7^th Edition):

Arora, Rohit. “Molecular mechanism of HIV-1 integrase inhibition by Raltegravir proposed by using of molecular modeling approaches : Mécanisme moléculaire de l'inhibition de l'intégrase du VIH-1 par le raltégravir proposé par l'utilisation d'approches de modélisation moléculaire.” 2012. Web. 20 Jan 2021.

Vancouver:

Arora R. Molecular mechanism of HIV-1 integrase inhibition by Raltegravir proposed by using of molecular modeling approaches : Mécanisme moléculaire de l'inhibition de l'intégrase du VIH-1 par le raltégravir proposé par l'utilisation d'approches de modélisation moléculaire. [Internet] [Doctoral dissertation]. Cachan, Ecole normale supérieure; 2012. [cited 2021 Jan 20]. Available from: http://www.theses.fr/2012DENS0055.

Council of Science Editors:

Arora R. Molecular mechanism of HIV-1 integrase inhibition by Raltegravir proposed by using of molecular modeling approaches : Mécanisme moléculaire de l'inhibition de l'intégrase du VIH-1 par le raltégravir proposé par l'utilisation d'approches de modélisation moléculaire. [Doctoral Dissertation]. Cachan, Ecole normale supérieure; 2012. Available from: http://www.theses.fr/2012DENS0055

Georgia State University

9. Li, Qiushi. Exploring HIV Integrase 3’-processing Using Designed DNA Substrates and Structural Study of HIV DNA Hairpins.

Degree: MS, Chemistry, 2016, Georgia State University

URL: https://scholarworks.gsu.edu/chemistry_theses/96

► In the HIV viral integration procedure, 3’-processing of the viral DNA by the integrase enzyme is an essential first step which is followed by… (more)

Subjects/Keywords: HIV Integrase; 3’-processing; DNA Substrates; Inosine

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Li, Q. (2016). Exploring HIV Integrase 3’-processing Using Designed DNA Substrates and Structural Study of HIV DNA Hairpins. (Thesis). Georgia State University. Retrieved from https://scholarworks.gsu.edu/chemistry_theses/96

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Li, Qiushi. “Exploring HIV Integrase 3’-processing Using Designed DNA Substrates and Structural Study of HIV DNA Hairpins.” 2016. Thesis, Georgia State University. Accessed January 20, 2021. https://scholarworks.gsu.edu/chemistry_theses/96.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Li, Qiushi. “Exploring HIV Integrase 3’-processing Using Designed DNA Substrates and Structural Study of HIV DNA Hairpins.” 2016. Web. 20 Jan 2021.

Vancouver:

Li Q. Exploring HIV Integrase 3’-processing Using Designed DNA Substrates and Structural Study of HIV DNA Hairpins. [Internet] [Thesis]. Georgia State University; 2016. [cited 2021 Jan 20]. Available from: https://scholarworks.gsu.edu/chemistry_theses/96.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Li Q. Exploring HIV Integrase 3’-processing Using Designed DNA Substrates and Structural Study of HIV DNA Hairpins. [Thesis]. Georgia State University; 2016. Available from: https://scholarworks.gsu.edu/chemistry_theses/96

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

10. Celso de Oliveira Rezende Júnior. SÍNTESE DE CANDIDATOS A NOVOS INIBIDORES DA ENZIMA HIV-INTEGRASE.

Degree: 2010, Universidade Federal de Juiz de Fora

URL: http://www.bdtd.ufjf.br/tde_busca/arquivo.php?codArquivo=849

► Este trabalho trata da síntese de cicloexanopoliois derivados do ácido quínico, esterificados com os ácidos cafeico e gálico. Esses compostos são candidatos a novos agentes… (more)

Subjects/Keywords: QUIMICA; HIV-integrase; Ácidos cafeoíl-quínicos; Cicloexanopoliois; Ácido cafeico; Ácido gálico; HIV-integrase; Caffeoyl quinic acid; Ciclohexanepoliols; Caffeic acid; Gallic acid

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Júnior, C. d. O. R. (2010). SÍNTESE DE CANDIDATOS A NOVOS INIBIDORES DA ENZIMA HIV-INTEGRASE. (Thesis). Universidade Federal de Juiz de Fora. Retrieved from http://www.bdtd.ufjf.br/tde_busca/arquivo.php?codArquivo=849

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Júnior, Celso de Oliveira Rezende. “SÍNTESE DE CANDIDATOS A NOVOS INIBIDORES DA ENZIMA HIV-INTEGRASE.” 2010. Thesis, Universidade Federal de Juiz de Fora. Accessed January 20, 2021. http://www.bdtd.ufjf.br/tde_busca/arquivo.php?codArquivo=849.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Júnior, Celso de Oliveira Rezende. “SÍNTESE DE CANDIDATOS A NOVOS INIBIDORES DA ENZIMA HIV-INTEGRASE.” 2010. Web. 20 Jan 2021.

Vancouver:

Júnior CdOR. SÍNTESE DE CANDIDATOS A NOVOS INIBIDORES DA ENZIMA HIV-INTEGRASE. [Internet] [Thesis]. Universidade Federal de Juiz de Fora; 2010. [cited 2021 Jan 20]. Available from: http://www.bdtd.ufjf.br/tde_busca/arquivo.php?codArquivo=849.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Júnior CdOR. SÍNTESE DE CANDIDATOS A NOVOS INIBIDORES DA ENZIMA HIV-INTEGRASE. [Thesis]. Universidade Federal de Juiz de Fora; 2010. Available from: http://www.bdtd.ufjf.br/tde_busca/arquivo.php?codArquivo=849

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

11. Oladosu, Oyindamola. Structures et fonctions du domaine C-Terminal de l'intégrase du VIH-1 : Structures and functions of the C-Terminal domain of HIV-1 integration.

Degree: Docteur es, Biophysique et biologie structurale, 2017, Université de Strasbourg

URL: http://www.theses.fr/2017STRAJ025

►

L’Integrase du VIH est une ADN recombinase catalysant deux réactions qui permettent l'intégration de l'ADN viral dans l'ADN hôte. L’intégrase du VIH comprend 3 domaines… (more)

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L’Integrase du VIH est une ADN recombinase catalysant deux réactions qui permettent l'intégration de l'ADN viral dans l'ADN hôte. L’intégrase du VIH comprend 3 domaines : N-terminal impliqué dans la réaction de « 3' processing » et le transfert de brin, le domaine catalytique contenant le site actif et le domaine C-terminal liant l'ADN non-spécifiquement (CTD). Des recherches récentes mettent en évidence l'importance du CTD dans la liaison avec d'autres protéines virales comme la transcriptase inverse. Le but de la thèse était de comprendre les rôles et l'importance du domaine C-terminal de l’intégrase dans deux contextes : l'intégration dans la chromatine et la coévolution, avec l'objectif de comprendre le rôle de la multimerisation dans la fonction de l’intégrase. Globalement, les résultats de mon projet indiquent que l'IN-CTD joue un rôle important, en contribuant à la formation de multimères d'ordre supérieur importants pour la fonction de l’IN.

HIV Integrase is a DNA recombinase that catalyzes two endonucleolytic reactions that allow the viral DNA integration into host DNA for replication and subsequent viral protein production. HIV Integrase consists of 3 structural and functional domains: The N-terminal zinc domain involved in 3’ processing and strand transfer, the catalytic core domain which contains the active site, and the C-terminal domain that binds DNA non- specifically. Recent research highlights the importance of the CTD in binding with other viral proteins such as Reverse Transcriptase. The aim of the thesis was to understand the roles and importance of the C-terminal domain of HIV-1 Integrase in two contexts: chromatin integration, and co-evolution, with the overall purpose of understanding the role of multimerization in IN function. Overall, results from my project indicate that the IN-CTD plays an important role, by contributing to the formation of higher order multimers that are important for IN functionality.

Advisors/Committee Members: Ruff, Marc (thesis director).

Subjects/Keywords: Integrase du VIH; Domaine C-terminal; Chromatine; Coévolution; Multimerisation; HIV Integrase; C-terminal domain; Chromatin; Coevolution; Multimerization; 572.8; 616.97

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Oladosu, O. (2017). Structures et fonctions du domaine C-Terminal de l'intégrase du VIH-1 : Structures and functions of the C-Terminal domain of HIV-1 integration. (Doctoral Dissertation). Université de Strasbourg. Retrieved from http://www.theses.fr/2017STRAJ025

Chicago Manual of Style (16^th Edition):

Oladosu, Oyindamola. “Structures et fonctions du domaine C-Terminal de l'intégrase du VIH-1 : Structures and functions of the C-Terminal domain of HIV-1 integration.” 2017. Doctoral Dissertation, Université de Strasbourg. Accessed January 20, 2021. http://www.theses.fr/2017STRAJ025.

MLA Handbook (7^th Edition):

Oladosu, Oyindamola. “Structures et fonctions du domaine C-Terminal de l'intégrase du VIH-1 : Structures and functions of the C-Terminal domain of HIV-1 integration.” 2017. Web. 20 Jan 2021.

Vancouver:

Oladosu O. Structures et fonctions du domaine C-Terminal de l'intégrase du VIH-1 : Structures and functions of the C-Terminal domain of HIV-1 integration. [Internet] [Doctoral dissertation]. Université de Strasbourg; 2017. [cited 2021 Jan 20]. Available from: http://www.theses.fr/2017STRAJ025.

Council of Science Editors:

Oladosu O. Structures et fonctions du domaine C-Terminal de l'intégrase du VIH-1 : Structures and functions of the C-Terminal domain of HIV-1 integration. [Doctoral Dissertation]. Université de Strasbourg; 2017. Available from: http://www.theses.fr/2017STRAJ025

UCLA

12. Xu, Xiaowen. Biochemical and Biophysical Characterization of the Interaction between Human Immunodeficiency Virus Type 1 Integrase and Capsid.

Degree: Bioengineering, 2017, UCLA

URL: http://www.escholarship.org/uc/item/4cg537w1

► Upon infection of host cells by human immunodeficiency virus type 1 (HIV-1), the viral membrane fuses with the cell plasma membrane and the viral core… (more)

Subjects/Keywords: Bioengineering; capsid; characterization; Human Immunodeficiency Virus Type 1; integrase; interaction

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Xu, X. (2017). Biochemical and Biophysical Characterization of the Interaction between Human Immunodeficiency Virus Type 1 Integrase and Capsid. (Thesis). UCLA. Retrieved from http://www.escholarship.org/uc/item/4cg537w1

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Xu, Xiaowen. “Biochemical and Biophysical Characterization of the Interaction between Human Immunodeficiency Virus Type 1 Integrase and Capsid.” 2017. Thesis, UCLA. Accessed January 20, 2021. http://www.escholarship.org/uc/item/4cg537w1.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Xu, Xiaowen. “Biochemical and Biophysical Characterization of the Interaction between Human Immunodeficiency Virus Type 1 Integrase and Capsid.” 2017. Web. 20 Jan 2021.

Vancouver:

Xu X. Biochemical and Biophysical Characterization of the Interaction between Human Immunodeficiency Virus Type 1 Integrase and Capsid. [Internet] [Thesis]. UCLA; 2017. [cited 2021 Jan 20]. Available from: http://www.escholarship.org/uc/item/4cg537w1.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Xu X. Biochemical and Biophysical Characterization of the Interaction between Human Immunodeficiency Virus Type 1 Integrase and Capsid. [Thesis]. UCLA; 2017. Available from: http://www.escholarship.org/uc/item/4cg537w1

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Toronto

13. Yamarte, Cesar. Generating Inducible Vector Systems for Controlling Pluripotent Stem Cell Fate.

Degree: 2012, University of Toronto

URL: http://hdl.handle.net/1807/33596

►

Transgenic manipulation of exogenous and endogenous gene expression in human embryonic stem cells (hESCs) is a powerful approach to decipher the genetic pathways dictating their… (more)

Subjects/Keywords: human embryonic stem cell; piggyBac; R4-Integrase; 0541

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Yamarte, C. (2012). Generating Inducible Vector Systems for Controlling Pluripotent Stem Cell Fate. (Masters Thesis). University of Toronto. Retrieved from http://hdl.handle.net/1807/33596

Chicago Manual of Style (16^th Edition):

Yamarte, Cesar. “Generating Inducible Vector Systems for Controlling Pluripotent Stem Cell Fate.” 2012. Masters Thesis, University of Toronto. Accessed January 20, 2021. http://hdl.handle.net/1807/33596.

MLA Handbook (7^th Edition):

Yamarte, Cesar. “Generating Inducible Vector Systems for Controlling Pluripotent Stem Cell Fate.” 2012. Web. 20 Jan 2021.

Vancouver:

Yamarte C. Generating Inducible Vector Systems for Controlling Pluripotent Stem Cell Fate. [Internet] [Masters thesis]. University of Toronto; 2012. [cited 2021 Jan 20]. Available from: http://hdl.handle.net/1807/33596.

Council of Science Editors:

Yamarte C. Generating Inducible Vector Systems for Controlling Pluripotent Stem Cell Fate. [Masters Thesis]. University of Toronto; 2012. Available from: http://hdl.handle.net/1807/33596

14. Adhya, Indranil. Exhaustive Identification of the retroelement Ty1 Integrase partners in yeast Saccharomyces cerevisiae : characterization of the role of Casein kinase II in Ty1 retrotransposition in vivo : Identification exhaustive de partenaires de l’intégrase du rétroélément Ty1 chez la levure Saccharomyces cerevisiae : caractérisation du rôle de la caséine kinase II dans la rétrotransposition de Ty1 in vivo.

Degree: Docteur es, Sciences de la vie et de la santé, 2018, Université Paris-Saclay (ComUE)

URL: http://www.theses.fr/2018SACLS589

►

Les rétrotransposons LTR sont des éléments transposables très répandus chez les eucaryotes. Comme les rétrovirus, ils se répliquent par transcription inverse de leur ARN en… (more)

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Les rétrotransposons LTR sont des éléments transposables très répandus chez les eucaryotes. Comme les rétrovirus, ils se répliquent par transcription inverse de leur ARN en ADNc, qui est intégré dans le génome hôte par leur propre intégrase (IN). Des études de séquençage à haut débit ont clairement établi que l'intégration ne se fait pas de façon aléatoire dans l'ensemble du génome de la cellule hôte. Des connaissances approfondies sur la biologie rétrovirale ont été acquises grâce à leur étude sur la levure utilisant le Ty1 LTR-retrotransposon comme modèle de travail. Le rétrotransposon Ty1 de la levure Saccharomyces cerevisiae intègre en amont des gènes de classe III, les gènes transcrits par l'ARN polymérase III (Pol III). Des données récentes ont révélé l'importance de l'AC40, une sous-unité de Pol III dans ce ciblage. Une interaction entre le Ty1 IN et l'AC40 est nécessaire pour le choix du site d'intégration des gènes Pol III. Néanmoins, le mécanisme moléculaire reste largement inconnu. Afin d'obtenir une vision globale de l'ensemble du phénomène qui se produit sur le site d'intégration, nous aimerions déterminer de manière exhaustive les protéines qui interagissent avec Ty1 IN et analyser leur rôle dans l'intégration de Ty1 et la transcription de l'ARN Pol III. Pour atteindre cet objectif, nous avons développé des approches protéomiques pour identifier de nouveaux partenaires cellulaires Ty1 intégraux. Nous avons identifié plusieurs nouveaux partenaires Ty1 IN qui semblent intéressants et leur rôle moléculaire dans la rétrotransposition de Ty1 sera étudié. Cependant, dans le cadre de mon doctorat, j'ai particulièrement travaillé à déchiffrer le rôle moléculaire de la protéine caséine kinase II dans la rétrotransposition de Ty1.

LTR-retrotransposons are widespread transposable elements in eukaryotes. Like retroviruses, they replicate by reverse transcription of their RNA into cDNA, which is integrated into the host genome by their own integrase (IN). High-throughput sequencing studies clearly established that integration does not occur randomly throughout the host-cell genome. Deep insights on retroviral biology have been gained by their study in yeast using the Ty1 LTR-retrotransposon as a working model. The Ty1 retrotransposon of the yeast Saccharomyces cerevisiae integrates upstream of class III genes, the genes transcribed by RNA polymerase III (Pol III). Recent data revealed the importance of AC40, a Pol III subunit in this targeting. An interaction between the Ty1 IN and AC40 is necessary for integration site choice at the Pol III genes. Nevertheless, the molecular mechanism remains largely unknown. To obtain a global view of the entire phenomenon that occurs on the integration site we would like to exhaustively determine the proteins that interact with Ty1 IN and analyze their role in both Ty1 integration and RNA Pol III transcription. To achieve this goal, we have developed proteomic approaches to identify new Ty1 integrase cellular partners. We have identified several novel Ty1 IN partners that seem…

Advisors/Committee Members: Acker, Joël (thesis director).

Subjects/Keywords: Ty1; Intégrase; TChAP; CK2; Rétroélément; Ty1; Integrase; TChAP; CK2; Retroelement

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Adhya, I. (2018). Exhaustive Identification of the retroelement Ty1 Integrase partners in yeast Saccharomyces cerevisiae : characterization of the role of Casein kinase II in Ty1 retrotransposition in vivo : Identification exhaustive de partenaires de l’intégrase du rétroélément Ty1 chez la levure Saccharomyces cerevisiae : caractérisation du rôle de la caséine kinase II dans la rétrotransposition de Ty1 in vivo. (Doctoral Dissertation). Université Paris-Saclay (ComUE). Retrieved from http://www.theses.fr/2018SACLS589

Chicago Manual of Style (16^th Edition):

Adhya, Indranil. “Exhaustive Identification of the retroelement Ty1 Integrase partners in yeast Saccharomyces cerevisiae : characterization of the role of Casein kinase II in Ty1 retrotransposition in vivo : Identification exhaustive de partenaires de l’intégrase du rétroélément Ty1 chez la levure Saccharomyces cerevisiae : caractérisation du rôle de la caséine kinase II dans la rétrotransposition de Ty1 in vivo.” 2018. Doctoral Dissertation, Université Paris-Saclay (ComUE). Accessed January 20, 2021. http://www.theses.fr/2018SACLS589.

MLA Handbook (7^th Edition):

Adhya, Indranil. “Exhaustive Identification of the retroelement Ty1 Integrase partners in yeast Saccharomyces cerevisiae : characterization of the role of Casein kinase II in Ty1 retrotransposition in vivo : Identification exhaustive de partenaires de l’intégrase du rétroélément Ty1 chez la levure Saccharomyces cerevisiae : caractérisation du rôle de la caséine kinase II dans la rétrotransposition de Ty1 in vivo.” 2018. Web. 20 Jan 2021.

Vancouver:

Adhya I. Exhaustive Identification of the retroelement Ty1 Integrase partners in yeast Saccharomyces cerevisiae : characterization of the role of Casein kinase II in Ty1 retrotransposition in vivo : Identification exhaustive de partenaires de l’intégrase du rétroélément Ty1 chez la levure Saccharomyces cerevisiae : caractérisation du rôle de la caséine kinase II dans la rétrotransposition de Ty1 in vivo. [Internet] [Doctoral dissertation]. Université Paris-Saclay (ComUE); 2018. [cited 2021 Jan 20]. Available from: http://www.theses.fr/2018SACLS589.

Council of Science Editors:

Adhya I. Exhaustive Identification of the retroelement Ty1 Integrase partners in yeast Saccharomyces cerevisiae : characterization of the role of Casein kinase II in Ty1 retrotransposition in vivo : Identification exhaustive de partenaires de l’intégrase du rétroélément Ty1 chez la levure Saccharomyces cerevisiae : caractérisation du rôle de la caséine kinase II dans la rétrotransposition de Ty1 in vivo. [Doctoral Dissertation]. Université Paris-Saclay (ComUE); 2018. Available from: http://www.theses.fr/2018SACLS589

15. Cosnefroy, Ophélie. L’Intégrase du VIH-1 : phosphorylation et caractérisation de partenaires cellulaires : HIV-1 Integrase : phosphorylation and cellular partners.

Degree: Docteur es, Sciences, technologie, santé. Microbiologie, 2011, Université de Bordeaux Segalen

URL: http://www.theses.fr/2011BOR21893

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L’intégrase (IN) du VIH-1 est une enzyme clé du cycle viral du VIH-1 puisque celle-ci catalyse l’insertion stable du génome viral dans celui de la… (more)

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L’intégrase (IN) du VIH-1 est une enzyme clé du cycle viral du VIH-1 puisque celle-ci catalyse l’insertion stable du génome viral dans celui de la cellule infectée. D’autre part, l’IN participe également à de nombreuses étapes du cycle viral (transcription inverse, import du complexe de préintégration, bourgeonnement…). L’étape d’intégration elle-même fait intervenir de nombreux partenaires cellulaires et viraux interagissant avec l’IN. Certains sont connus et étudiés (LEDGF/P75, TNPO3…), mais il est très probable qu’un très grand nombre de ces partenaires soient encore méconnus malgré leur importance. Depuis quelque année, le rôle des modifications post-traductionnelles de l’IN a commencé à être étudié. En effet plusieurs études montrent que la régulation de l’activité de l’IN pourrait se faire via de telles modifications. Mon travail de thèse s’est orienté sur trois questions autour de ces deux aspects. -Nous avons identifié plusieurs phosphorylations de l’IN par spectrométrie de masse et mis en évidence le rôle essentiel de la phopshorylation de la sérine 24 pour l’infection virale. -Le rôle de la kinase cellulaire GCN2 a été étudié. Nous avons pu montrer un effet restrictif de la protéine sur le cycle viral amenant à un arrêt de la traduction à un temps court après l’infection au VIH-1. L’interaction entre GCN2 et l’IN a été mise en évidence. L’étude du domaine d’interaction entre l’IN et GCN2 a permis la caractérisation d’un résidu essentiel de l’IN, le E85. -L’impact du facteur de réparation RAD51 sur la réplication virale a été étudié. Nous avons montré un effet inhibiteur de cette protéine. Ce travail a permis l’identification d’une molécule chimique RS-1 capable d’inhiber l’intégration dans les cellules infectées via la stimulation de RAD51.

The integrase (IN) of HIV-1 is a key enzyme of the viral cycle of HIV-1 since it catalyzes the stable integration of the viral genome into that of the infected cell. Furthermore, the IN also participates in many steps of the viral cycle (reverse transcription, import of preintegration complex, budding ...). The integration step itself involves many cellular and viral partners interacting with IN. Some of them are studied (LEDGF/p75, TNPO3 ...) but it is very likely that many of these partners are still unknown despite their importance. Recently, the role of post-translational modifications of the IN began to be studied. In fact several studies show that the regulation of the activity of IN could be done through such modifications.My thesis work focused on three issues: -We identified several phosphorylations of IN by mass spectrometry and identified the crucial role of serine 24 to viral infection. -The role of GCN2 cellular kinase was studied. We have shown a restrictive effect of the protein on the viral cycle leading to a translation stop in first hours following infection with HIV-1. The study of the interaction domain between IN and GCN2 allowed the characterization of a critical residue of IN, the E85. -The impact of RAD51 repair factor on viral replication was…

Advisors/Committee Members: Andréola, Marie-Line (thesis director).

Subjects/Keywords: VIH; Intégrase; Phosphorylation; GCN2; RAD51; HIV; Integrase; Phosphorylation; GCN2; RAD51

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Cosnefroy, O. (2011). L’Intégrase du VIH-1 : phosphorylation et caractérisation de partenaires cellulaires : HIV-1 Integrase : phosphorylation and cellular partners. (Doctoral Dissertation). Université de Bordeaux Segalen. Retrieved from http://www.theses.fr/2011BOR21893

Chicago Manual of Style (16^th Edition):

Cosnefroy, Ophélie. “L’Intégrase du VIH-1 : phosphorylation et caractérisation de partenaires cellulaires : HIV-1 Integrase : phosphorylation and cellular partners.” 2011. Doctoral Dissertation, Université de Bordeaux Segalen. Accessed January 20, 2021. http://www.theses.fr/2011BOR21893.

MLA Handbook (7^th Edition):

Cosnefroy, Ophélie. “L’Intégrase du VIH-1 : phosphorylation et caractérisation de partenaires cellulaires : HIV-1 Integrase : phosphorylation and cellular partners.” 2011. Web. 20 Jan 2021.

Vancouver:

Cosnefroy O. L’Intégrase du VIH-1 : phosphorylation et caractérisation de partenaires cellulaires : HIV-1 Integrase : phosphorylation and cellular partners. [Internet] [Doctoral dissertation]. Université de Bordeaux Segalen; 2011. [cited 2021 Jan 20]. Available from: http://www.theses.fr/2011BOR21893.

Council of Science Editors:

Cosnefroy O. L’Intégrase du VIH-1 : phosphorylation et caractérisation de partenaires cellulaires : HIV-1 Integrase : phosphorylation and cellular partners. [Doctoral Dissertation]. Université de Bordeaux Segalen; 2011. Available from: http://www.theses.fr/2011BOR21893

16. Jaspart, Anaïs. Protéine kinase GCN2 et phosphorylation de l’intégrase du VIH-1 : Kinase GCN2 and the phosphorylation of HIV-1 integrase.

Degree: Docteur es, Microbiologie-Immunologie, 2014, Bordeaux

URL: http://www.theses.fr/2014BORD0405

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L’intégrase (IN) du VIH-1 est une enzyme clé qui catalyse l’insertion stable du génome viral dans celui de la celluleinfectée. D’autre part, l’IN participe également… (more)

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L’intégrase (IN) du VIH-1 est une enzyme clé qui catalyse l’insertion stable du génome viral dans celui de la celluleinfectée. D’autre part, l’IN participe également à de nombreuses étapes du cycle viral telles que la transcriptioninverse ou la maturation virale. La compréhension des mécanismes impliqués dans la régulation de l’intégrationcellulaire au cours de l’infection est un enjeu important. L’IN fait partie du complexe de préintégration composé defacteurs cellulaires et viraux. La dynamique des interactions au sein de ce complexe régule les activités catalytiquesmais également non catalytiques de l’IN. C’est dans ce contexte de recherche de nouveaux cofacteurs de l’intégraseque nous avons identifié une interaction entre l’IN et la protéine Kinase GCN2.Mon travail de thèse s’est orienté sur trois questions autour de l’étude du rôle de cette interaction IN/GCN2.- Dans un premier temps, le rôle de la protéine kinase cellulaire GCN2 au cours du cycle viral a été étudié. Nousavons pu montrer que l’infection par le VIH-1 provoque un stress activant GCN2. Cette activation aboutit à uneinhibition de la traduction dès les premières heures de l’infection.- GCN2 est capable de phosphoryler l’IN du VIH-1 sur deux positions : les sérines en position 24 et 255. L’étude durôle de la phosphorylation de l’IN par GCN2 a permis de montrer que l’absence de phosphorylation de l’IN entraîneune stimulation de l’infection. GCN2 via la phosphorylation de l’IN a donc un effet restrictif sur l’infection par le VIH-1.- L’étude du domaine d’interaction entre l’IN et GCN2 a permis d’identifier un résidu essentiel de l’IN, l’acideglutamique en position 85 (E85). En effet, la mutation E85A de l’IN entraîne la production de virus non infectieux,suite à un défaut de maturation

HIV-1 integrase (IN) catalyzes the integration of the viral DNA into the cellular genome. Besides, IN is also involved inother steps of the viral life cycle like the reverse transcription or the viral maturation. Our group is interested in themechanisms involved in the regulation of cellular integration during the infection. IN is part of a pre-integrationcomplex composed of cellular and viral proteins. The dynamic of these interactions regulates IN activities but also noncatalytic activities such as nuclear import and tethering of the complex to the integration site. During theidentification of news partners of IN, an interaction between IN and the kinase GCN2 was characterizedMy PhD project is composed of 3 topics:- The role of the cellular kinase GCN2 was studied during the viral cycle. We showed that GCN2 is activated uponHIV-1 infection. This activation leads to a general decrease of cellular translation during the first hours of infection.-GCN2 is able to phosphorylate IN on two positions: the serines in position 24 and 255. The absence of INphosphorylation causes a stimulation of HIV-1 infection. We demonstrate that GCN2 affects the viral cycle via thephosphorylation of IN.- Binding domain analysis between IN and GCN2 led to the identification of a critical…

Advisors/Committee Members: Andréola, Marie-Line (thesis director).

Subjects/Keywords: VIH-1; Intégrase; GCN2; HIV-1; Integrase; GCN2

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Jaspart, A. (2014). Protéine kinase GCN2 et phosphorylation de l’intégrase du VIH-1 : Kinase GCN2 and the phosphorylation of HIV-1 integrase. (Doctoral Dissertation). Bordeaux. Retrieved from http://www.theses.fr/2014BORD0405

Chicago Manual of Style (16^th Edition):

Jaspart, Anaïs. “Protéine kinase GCN2 et phosphorylation de l’intégrase du VIH-1 : Kinase GCN2 and the phosphorylation of HIV-1 integrase.” 2014. Doctoral Dissertation, Bordeaux. Accessed January 20, 2021. http://www.theses.fr/2014BORD0405.

MLA Handbook (7^th Edition):

Jaspart, Anaïs. “Protéine kinase GCN2 et phosphorylation de l’intégrase du VIH-1 : Kinase GCN2 and the phosphorylation of HIV-1 integrase.” 2014. Web. 20 Jan 2021.

Vancouver:

Jaspart A. Protéine kinase GCN2 et phosphorylation de l’intégrase du VIH-1 : Kinase GCN2 and the phosphorylation of HIV-1 integrase. [Internet] [Doctoral dissertation]. Bordeaux; 2014. [cited 2021 Jan 20]. Available from: http://www.theses.fr/2014BORD0405.

Council of Science Editors:

Jaspart A. Protéine kinase GCN2 et phosphorylation de l’intégrase du VIH-1 : Kinase GCN2 and the phosphorylation of HIV-1 integrase. [Doctoral Dissertation]. Bordeaux; 2014. Available from: http://www.theses.fr/2014BORD0405

17. Chahpazoff, Margaux. Étude moléculaire et structurale de l’intégrase du virus porcin PERV et de son partenaire cellulaire humain Brd2, dans le cadre de la prévention de xénozoonoses rétrovirales : Molecular and structural study of Porcin Endogenous RetroVirus integrase and its human cellular cofactor Brd2, for the prevention of retroviral xenozoonosis.

Degree: Docteur es, Biochimie, 2020, Lyon

URL: http://www.theses.fr/2020LYSE1003

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L’utilisation d’organes porcins pourrait pallier le déficit d’organes humains pour les patients en attente de greffe. Le développement de cette technique est cependant limité par… (more)

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L’utilisation d’organes porcins pourrait pallier le déficit d’organes humains pour les patients en attente de greffe. Le développement de cette technique est cependant limité par la présence d’un rétrovirus endogène actif dans le génome des cellules porcines. L’intégrase (IN) du rétrovirus recombinant endogène porcin PERV-A/C catalyse une étape clé du cycle rétroviral et constitue une cible thérapeutique de choix. Cette IN utilise un cofacteur cellulaire, la protéine Brd2, qui permet le ciblage de sites d’intégration spécifiques et une infection productive. La première partie du manuscrit porte sur l’étude biochimique et structurale de la zone d’interaction entre l’IN de PERV-A/C et la protéine Brd2 humaine. Des acides aminés essentiels pour l’interaction ont été caractérisés et une enveloppe SAXS a été déterminée. Ces résultats ont permis de mieux comprendre le mécanisme d’interaction et de proposer un modèle structural de l’intasome des Gammarétrovirus avec un fragment de Brd2 lié. Un protocole de purification de cet assemblage macromoléculaire a ensuite été mis au point et des images de microscopie électronique ont été enregistrées. Un criblage de molécules candidates pour inhiber la formation du complexe intasome:Brd2 a également été réalisé, dans le but de développer une thérapie réduisant les risques de xénozoonose

Xenotransplantation is the transplantation of organs, tissues or cells from an animal to a human recipient and appears to be a promising option regarding the lack of human donors. Research is now focusing on pig donors, but this animal carries an active endogenous Gammaretrovirus, termed PERV (Porcin Endogenous RetroVirus), able to infect patients. Recombinant PERV-A/C IN is a key enzyme of the retroviral life cycle and a relevant therapeutic target. IN requires a cellular cofactor, the human protein Brd2, which allows to target specific integration sites and is mandatory for a productive infection. During this thesis, residues essential for the IN:Brd2 interaction were identified and a SAXS envelope of a two fragments complex were determined. With the support of these experimental results, a first model of the gammaretroviral intasome with a bound Brd2 fragment was built. Finally, a purification protocol of this macromolecular assembly was set-up and electron microscopy images were collected. A first screening of putative IN:Brd2 interaction modulators was carried out with the purpose of developing a therapy limiting xenozoonosis risks

Advisors/Committee Members: Gouet, Patrice (thesis director).

Subjects/Keywords: Rétrovirus; Intégrase; Brd2; PERV; Xénotransplantation; Retrovirus; Integrase; Brd2; PERV; Xenotransplantation; 570

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Chahpazoff, M. (2020). Étude moléculaire et structurale de l’intégrase du virus porcin PERV et de son partenaire cellulaire humain Brd2, dans le cadre de la prévention de xénozoonoses rétrovirales : Molecular and structural study of Porcin Endogenous RetroVirus integrase and its human cellular cofactor Brd2, for the prevention of retroviral xenozoonosis. (Doctoral Dissertation). Lyon. Retrieved from http://www.theses.fr/2020LYSE1003

Chicago Manual of Style (16^th Edition):

Chahpazoff, Margaux. “Étude moléculaire et structurale de l’intégrase du virus porcin PERV et de son partenaire cellulaire humain Brd2, dans le cadre de la prévention de xénozoonoses rétrovirales : Molecular and structural study of Porcin Endogenous RetroVirus integrase and its human cellular cofactor Brd2, for the prevention of retroviral xenozoonosis.” 2020. Doctoral Dissertation, Lyon. Accessed January 20, 2021. http://www.theses.fr/2020LYSE1003.

MLA Handbook (7^th Edition):

Chahpazoff, Margaux. “Étude moléculaire et structurale de l’intégrase du virus porcin PERV et de son partenaire cellulaire humain Brd2, dans le cadre de la prévention de xénozoonoses rétrovirales : Molecular and structural study of Porcin Endogenous RetroVirus integrase and its human cellular cofactor Brd2, for the prevention of retroviral xenozoonosis.” 2020. Web. 20 Jan 2021.

Vancouver:

Chahpazoff M. Étude moléculaire et structurale de l’intégrase du virus porcin PERV et de son partenaire cellulaire humain Brd2, dans le cadre de la prévention de xénozoonoses rétrovirales : Molecular and structural study of Porcin Endogenous RetroVirus integrase and its human cellular cofactor Brd2, for the prevention of retroviral xenozoonosis. [Internet] [Doctoral dissertation]. Lyon; 2020. [cited 2021 Jan 20]. Available from: http://www.theses.fr/2020LYSE1003.

Council of Science Editors:

Chahpazoff M. Étude moléculaire et structurale de l’intégrase du virus porcin PERV et de son partenaire cellulaire humain Brd2, dans le cadre de la prévention de xénozoonoses rétrovirales : Molecular and structural study of Porcin Endogenous RetroVirus integrase and its human cellular cofactor Brd2, for the prevention of retroviral xenozoonosis. [Doctoral Dissertation]. Lyon; 2020. Available from: http://www.theses.fr/2020LYSE1003

University of Illinois – Urbana-Champaign

18. Kim, Seyeun. Structure-function analysis of IntDOT, the CTnDOT integrase.

Degree: PhD, 0322, 2011, University of Illinois – Urbana-Champaign

URL: http://hdl.handle.net/2142/18325

► IntDOT is an enzyme required for the recombination reactions that promote movement of CTnDOT that is an integrative conjugative element (ICE) found in Bacteroides spp.… (more)

▼ IntDOT is an enzyme required for the recombination reactions that promote movement of CTnDOT that is an integrative conjugative element (ICE) found in Bacteroides spp. IntDOT has been classified in the tyrosine recombinase family. However, unlike most other tyrosine recombinases that require sequence identity in the region where strand exchanges occur, IntDOT recombines overlap sequences that contain mismatched base pairs. Therefore, IntDOT uses different mechanisms from those of other tyrosine recombinases. IntDOT has three DNA binding domains, the N terminus arm (N) domain, the core binding (CB) domain, the catalytic (CAT) domain. The CAT and CB domain bind to the core type sites and the N domain binds to the arm-type sites that are distantly located from the core-type sites. The CAT domain is the most conserved domain among members of the tyrosine recombinase family and contains six catalytic signature residues, R1KHIRIIHIIY, IntDOT, however, has serine residue in the place of the first catalytic arginine, R1. I performed a mutational analysis of IntDOT protein and isolated mutants with substitutions in all three domains of IntDOT proteins, I constructed an E.coli indicator strain that employs the lacI gene as a reporter. The in vivo integration assay using the E.coli indicator strain enables screening for IntDOT mutants from a large population containing random mutations. I isolated twenty five IntDOT mutants that are defective in integration. Four substitutions contained substitutions int eh N domain, two contained substitutions in the CB domain, and the nineteen contained substitutions in the CAT domain. Biochemical assays such as DNA binding, cleavage, and ligation were used to characterize IntDOT functions to determine which steps in the recombination pathway were defective. The results show that the IntDOT N domain is not required for cleavage and ligation but is important for binding to the arm-type sites. In the CAT domain, residue A352 is likely to be important for positioning the catalytic tyrosine, Y381, in the active site. Residue R285 could provide the missing function of the R1 residue in catalysis. Durign recombination, four IntDOT monomers perform two sets of sequential strand exchanges. The first set of strand exchanges forms the Holliday Junction (HJ) intermediate and the second set of strand exchanges resolves the HJ to complete the recombination reaction. During formation and resolution of the HJ, the four IntDOT monomers communicate with each other and coordinate the resolution fo the HJ intermediate. To study protein-protein interactions formed between IntDOT monomers, I developed an HJ in vitro resolution assay using synthetic HJs. I constructed two different types of HJs by designing oligos lacking the arm-type sites but containing the core-type sites. One HJ contains identical overlap sequences as si found in most tyrosine recombinase systems. The other HJ contains mismatched overlap sequences as found in natural attDOT and attB sites. I analyzed resolution of… Advisors/Committee Members: Gardner, Jeffrey F. (advisor), Gardner, Jeffrey F. (Committee Chair), Slauch, James M. (committee member), Blanke, Steven R. (committee member), Vanderpool, Carin K. (committee member).

Subjects/Keywords: Tyrosine recombinase family; Bacteroides conjugative transposon (CTnDOT); CTnDOT integrase (IntDOT)

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Kim, S. (2011). Structure-function analysis of IntDOT, the CTnDOT integrase. (Doctoral Dissertation). University of Illinois – Urbana-Champaign. Retrieved from http://hdl.handle.net/2142/18325

Chicago Manual of Style (16^th Edition):

Kim, Seyeun. “Structure-function analysis of IntDOT, the CTnDOT integrase.” 2011. Doctoral Dissertation, University of Illinois – Urbana-Champaign. Accessed January 20, 2021. http://hdl.handle.net/2142/18325.

MLA Handbook (7^th Edition):

Kim, Seyeun. “Structure-function analysis of IntDOT, the CTnDOT integrase.” 2011. Web. 20 Jan 2021.

Vancouver:

Kim S. Structure-function analysis of IntDOT, the CTnDOT integrase. [Internet] [Doctoral dissertation]. University of Illinois – Urbana-Champaign; 2011. [cited 2021 Jan 20]. Available from: http://hdl.handle.net/2142/18325.

Council of Science Editors:

Kim S. Structure-function analysis of IntDOT, the CTnDOT integrase. [Doctoral Dissertation]. University of Illinois – Urbana-Champaign; 2011. Available from: http://hdl.handle.net/2142/18325

19. Kashani Moghaddam, Matinehalsadat. Improving HIV-1 Integrase Inhibitors Prediction Using Hybrid Differential Evolution-Binary Particle Swarm Algorithm .

Degree: 2015, California State University – San Marcos

URL: http://hdl.handle.net/10211.3/139174

► Due to the mutation of HIV enzymes and their resistance against current drugs, drug companies are exploring ways to develop stronger mutant resistant drugs. Dimeric… (more)

Subjects/Keywords: DE-BPSO; Linear Models; HIV-1 Integrase Inhibitors

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Kashani Moghaddam, M. (2015). Improving HIV-1 Integrase Inhibitors Prediction Using Hybrid Differential Evolution-Binary Particle Swarm Algorithm . (Thesis). California State University – San Marcos. Retrieved from http://hdl.handle.net/10211.3/139174

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Kashani Moghaddam, Matinehalsadat. “Improving HIV-1 Integrase Inhibitors Prediction Using Hybrid Differential Evolution-Binary Particle Swarm Algorithm .” 2015. Thesis, California State University – San Marcos. Accessed January 20, 2021. http://hdl.handle.net/10211.3/139174.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Kashani Moghaddam, Matinehalsadat. “Improving HIV-1 Integrase Inhibitors Prediction Using Hybrid Differential Evolution-Binary Particle Swarm Algorithm .” 2015. Web. 20 Jan 2021.

Vancouver:

Kashani Moghaddam M. Improving HIV-1 Integrase Inhibitors Prediction Using Hybrid Differential Evolution-Binary Particle Swarm Algorithm . [Internet] [Thesis]. California State University – San Marcos; 2015. [cited 2021 Jan 20]. Available from: http://hdl.handle.net/10211.3/139174.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Kashani Moghaddam M. Improving HIV-1 Integrase Inhibitors Prediction Using Hybrid Differential Evolution-Binary Particle Swarm Algorithm . [Thesis]. California State University – San Marcos; 2015. Available from: http://hdl.handle.net/10211.3/139174

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

20. Slaughter, Alison Paige. Mechanism of action of allosteric HIV-1 integrase inhibitors.

Degree: PhD, Pharmacy, 2015, The Ohio State University

URL: http://rave.ohiolink.edu/etdc/view?acc_num=osu1428684473

► An essential step in the HIV-1 replication cycle is the integration of the viral DNA into the host chromatin, which is catalyzed by the viral… (more)

▼ An essential step in the HIV-1 replication cycle is the integration of the viral DNA into the host chromatin, which is catalyzed by the viral enzyme integrase (IN). The cellular cofactor lens epithelial growth factor (LEDGF)/p75 plays a significant role in integration by acting as a bimodal tether between IN and chromatin. These interactions are crucial for HIV-1 replication and present attractive targets for antiviral therapy. Herein, I will present research aimed at dissecting the mechanism of action of novel allosteric HIV-1 IN inhibitors. Chapter 1 introduces HIV-1 IN biology, function and its inhibition. This chapter will focus on the structural biology and function of HIV-1 IN. The role of LEDGF/p75 in replication and integration site selection will be discussed. Finally, the chapter will discuss three mechanisms of IN inhibition: (I) FDA approved active site inhibitors; (2) IN multimerization as a therapeutic target; and (3) IN-LEDGF/p75 binding as a drug target.Chapter 2 presents the findings that novel allosteric HIV-1 IN inhibitors (ALLINIs) have a multimodal mechanism of action. We demonstrate that this class of compounds impairs both IN-LEDGF/p75 binding and LEDGF/p75-independent IN catalytic activities with similar IC50 values, defining them as bona fide allosteric inhibitors of IN function. Our findings argue strongly that improved ALLINI derivatives could exhibit desirable clinical properties.Chapters 3 and 4 dissect the structural and mechanistic basis for resistance to ALLINIs. The A128T IN and H171T IN substitution emerges under ALLINI-1 and BI-D selective pressure, respectively. Chapter 3 demonstrates that the A128T substitution does not affect inhibitor binding but alters the positioning of the inhibitor at the IN dimer interface. As a result, ALLINIs are no longer able to promote aberrant higher order IN oligomers. We conclude that ALLINIs primarily target IN multimerization rather than IN-LEDGF/p75 binding. Chapter 4 shows that the H171T substitution significantly reduces the affinity for BI-D binding to recombinant H171T IN CCD. X-ray crystal structures coupled with binding free energy calculations reveal the importance of the Nd- protonated imidazole group of His171 for high affinity BI-D binding. These findings reveal a distinct mechanism of resistance for the H171T IN mutation to ALLINI BI-D. Chapter 5 presents the design of small molecules that allowed us to probe the role of HIV-1 IN multimerization independently from IN-LEDGF/p75 interactions in infected cells. The most potent multimerization selective inhibitor potently blocks HIV-1 replication by inducing aberrant IN multimerization in virus particles. These findings delineate the significance of correctly ordered IN structure for HIV-1 particle morphogenesis and present a novel class of multimerization selective IN inhibitors as investigational probes for HIV-1 molecular biology.Finally, chapter 6 summarizes the findings and significance of this dissertation research as well as provides future perspectives. In summary, this… Advisors/Committee Members: Kvaratskhelia, Mamuka (Advisor).

Subjects/Keywords: Pharmacy Sciences; Virology; HIV Integrase; LEDGF; Allosteric inhibitors; Drug Resistance

10 more images…

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Slaughter, A. P. (2015). Mechanism of action of allosteric HIV-1 integrase inhibitors. (Doctoral Dissertation). The Ohio State University. Retrieved from http://rave.ohiolink.edu/etdc/view?acc_num=osu1428684473

Chicago Manual of Style (16^th Edition):

Slaughter, Alison Paige. “Mechanism of action of allosteric HIV-1 integrase inhibitors.” 2015. Doctoral Dissertation, The Ohio State University. Accessed January 20, 2021. http://rave.ohiolink.edu/etdc/view?acc_num=osu1428684473.

MLA Handbook (7^th Edition):

Slaughter, Alison Paige. “Mechanism of action of allosteric HIV-1 integrase inhibitors.” 2015. Web. 20 Jan 2021.

Vancouver:

Slaughter AP. Mechanism of action of allosteric HIV-1 integrase inhibitors. [Internet] [Doctoral dissertation]. The Ohio State University; 2015. [cited 2021 Jan 20]. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=osu1428684473.

Council of Science Editors:

Slaughter AP. Mechanism of action of allosteric HIV-1 integrase inhibitors. [Doctoral Dissertation]. The Ohio State University; 2015. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=osu1428684473

21. Carvalho, Luciana Luzia de. Modelagem molecular de uma série de compostos inibidores da enzima integrase do vírus HIV-1.

Degree: PhD, Físico-Química, 2011, University of São Paulo

URL: http://www.teses.usp.br/teses/disponiveis/75/75131/tde-16092011-160536/ ;

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Uma etapa essencial no ciclo de vida do vírus HIV é a integração do DNA viral no cromossomo hospedeiro. Essa etapa é catalisada pela enzima… (more)

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Uma etapa essencial no ciclo de vida do vírus HIV é a integração do DNA viral no cromossomo hospedeiro. Essa etapa é catalisada pela enzima integrase (IN) de 32-kDa. HIV-1 IN é um importante e validado alvo, e as drogas que inibem seletivamente a enzima, quando utilizadas em combinação com os inibidores da transcriptase reversa (RT) e protease (PR), são consideradas altamente eficazes em suprimir a replicação viral. IN catalisa dois processos enzimáticos designados por 3ṕrocessamento e transferência de DNA. Agentes ativos contra integrase, inibindo a etapa de transferência da vertente já estão em fase clínica. O fármaco Raltegravir® é o primeiro nesta nova classe. Os ensaios clínicos no tratamento em novos pacientes têm uma atividade anti-retroviral potente e bem tolerado. Dada a sua potência, segurança e novo mecanismo de ação, os inibidores da integrase representam um importante avanço terapêutico contra o HIV-1. Na presente tese de doutorado, foram realizados estudos quimiométricos utilizando descritores teóricos e QSAR bi- (2D) e tridimensionais (3D) empregando, respectivamente, as técnicas holograma QSAR (HQSAR) e a análise comparativa dos campos moleculares (CoMFA), visando à geração de modelos preditivos para um conjunto de inibidores da integrase do vírus HIV-1. Modelos de QSAR com boa consistência interna, habilidade preditiva e estabilidade foram obtidos em todos os casos. Os modelos gerados, associados às informações obtidas pelos mapas de contribuição 2D e de contorno 3D, são guias químico-medicinais úteis no planejamento de novos inibidores mais potentes e seletivos da integrase do HIV-1.

An essential step in the HIV life cycle is integration of the viral DNA into the host chromosome. This step is catalyzed by a 32-kDa viral enzyme HIV integrase (IN). HIV-1 IN is an important and validated target, and the drugs that selectively inhibit this enzyme, when used in combination with reverse transcriptase (RT) and protease (PR) inhibitors, are believed to be highly effective in suppressing the viral replication. IN catalyzes two discrete enzymatic processes referred as 3ṕrocessing and DNA strand transfer. Agents active against HIV-1, which target the viral integrase by inhibiting the strand transfer step of integration, have now initialized the clinical trials. The Raltegravir® is the first drug in this new class. Clinical trials in treatment-experienced and in treatment-naive patients have shown that raltegravir-containing regimens have potent antiretroviral activity and are well tolerated. Given their potency, safety and novel mechanism of action, integrase inhibitors represent an important advance in HIV-1 therapy. In the present thesis, Bi- and Tridimensional Quantitative Structure-Activity Relationship (QSAR) studies were performed applying chemometric methods based on theoretical descriptors, Comparative Molecular Field Analysis (CoMFA) and Holograma QSAR (HQSAR) techniques, aiming to generate predictive models for a large set of HIV-1 IN inhibitors. QSAR models presenting good internal…

Advisors/Committee Members: Silva, Albérico Borges Ferreira da.

Subjects/Keywords: CoMFA; CoMFA; Docking molecular; HIV-I; HIV-I; HQSAR; HQSAR; Integrase; Integrase HIV-I; Molecular Docking; QSAR; QSAR; QSAR-3D; QSAR-3D

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Carvalho, L. L. d. (2011). Modelagem molecular de uma série de compostos inibidores da enzima integrase do vírus HIV-1. (Doctoral Dissertation). University of São Paulo. Retrieved from http://www.teses.usp.br/teses/disponiveis/75/75131/tde-16092011-160536/ ;

Chicago Manual of Style (16^th Edition):

Carvalho, Luciana Luzia de. “Modelagem molecular de uma série de compostos inibidores da enzima integrase do vírus HIV-1.” 2011. Doctoral Dissertation, University of São Paulo. Accessed January 20, 2021. http://www.teses.usp.br/teses/disponiveis/75/75131/tde-16092011-160536/ ;.

MLA Handbook (7^th Edition):

Carvalho, Luciana Luzia de. “Modelagem molecular de uma série de compostos inibidores da enzima integrase do vírus HIV-1.” 2011. Web. 20 Jan 2021.

Vancouver:

Carvalho LLd. Modelagem molecular de uma série de compostos inibidores da enzima integrase do vírus HIV-1. [Internet] [Doctoral dissertation]. University of São Paulo; 2011. [cited 2021 Jan 20]. Available from: http://www.teses.usp.br/teses/disponiveis/75/75131/tde-16092011-160536/ ;.

Council of Science Editors:

Carvalho LLd. Modelagem molecular de uma série de compostos inibidores da enzima integrase do vírus HIV-1. [Doctoral Dissertation]. University of São Paulo; 2011. Available from: http://www.teses.usp.br/teses/disponiveis/75/75131/tde-16092011-160536/ ;

Université Montpellier II

22. Moustapha Abba Moussa, Daouda. Développement d'inhibiteurs de la dimérisation du complexe de la Reverse Transcription du VIH-1 : Dimerization of HIV-1 Reverse Transcriptase as a potent target to block HIV replication.

Degree: Docteur es, Biologie Santé, 2013, Université Montpellier II

URL: http://www.theses.fr/2013MON20238

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Le virus de l'immunodéficience humain de type 1 VIH-1 est un rétrovirus responsable d'une pandémie touchant actuellement 34 millions de personnes dont près de 25… (more)

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Le virus de l'immunodéficience humain de type 1 VIH-1 est un rétrovirus responsable d'une pandémie touchant actuellement 34 millions de personnes dont près de 25 millons en sont morts. En dépit des grands progrès réalisés dans le développement de nouveaux médicaments visant à bloquer la réplication de ce virus, l'émergence rapide de souches virales mutantes résistantes imposent l'urgence et la nécessité de développer de nouvelles stratégies thérapeutiques pour combattre ce virus. La Reverse Transcriptase (RT) duVIH-1 joue un rôle majeur dans le cycle viral puisqu'elle est responsable de convertir l'ARN génomique simple brin en ADN double afin d'intégrer l'ADN génomique de la cellule hôte. La forme biologique de la RT est un hétérodimère formé de la sous unité p66 et la sous unité p51. Les sous unités sont constituées des sous domaines fingers, palm, « connection », thumb et RNase H, ce dernier étant absent sur la sous unité p51. L'activation de la RT est un processus en deux étapes : la première étape consiste en l'association rapide des deux sous unités, suivie d'une deuxième étape plus lente, correspondant à des changements conformationnels fins à l'interface entre p66/p51.Dans l'objectif d'inhiber la fonction de la RT, nous avons proposé une nouvelle stratégie fondée sur l'utilisation des peptides interfacials courts dérivant de séquences hautement conserver de la RT, capables de cibler efficacement les interactions protéine/protéine et de bloquer la dimérisation et l'activation par maturation de la RT. La dimérisation des deux sous unités implique leur interaction part les domaines de connexion. Dans la première partie de ce travail de thèse, nous avons criblé et isolé des peptides capables d'interférer avec cette interaction impliquant un « cluster » de résidus aromatiques. Nous avons identifié un peptide court PID4, et démontré que ce peptide induit un changement de conformation de la RT, entrainant la dissociation du complexe. La maturation implique l'interaction de résidus localisés au niveau de « hot spot » dans le domaine RNase H de p66 et thumb de p51. Dans la deuxième partie de cette thèse, nous avons sélectionné un peptide court, P27, issus du domaine thumb pouvant inhiber l'étape de la « maturation » (P27). Ces deux classes de peptides bloquent la réplication virale et sont efficaces sur plusieurs souches virales et sur des mutants résistants aux NNRTIS et NRTIS.Les résultats obtenus sur nos deux classes d'inhibiteurs peptidiques, démontrent bien que la dimérisation et la maturation de la RT constituent des cibles de choix pour bloquer l'activité polymérase de la RT et ainsi stopper la prolifération virale par un nouvel concept moins exposer à l'émergence des mutation de résistance.

The human immunodeficiency virus type 1 (HIV-1) is a retrovirus responsible of a disease currently affecting 34 million people and caused the death of 25 million people from its discovery in the 1980s. Despite the great progresses made in the development of new drugs to block the replication of the virus, the rapid…

Advisors/Committee Members: Divita, Gilles (thesis director).

Subjects/Keywords: Vih-1; Reverse Transcriptase; Integrase; Inhibiteurs peptidiques; Résistance; Dimérisation et maturation du VIH; Hiv-1; Reverse Transcriptase; Integrase; Peptides inhibitors; Resistance; Dimerization and maturation of HIV

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Moustapha Abba Moussa, D. (2013). Développement d'inhibiteurs de la dimérisation du complexe de la Reverse Transcription du VIH-1 : Dimerization of HIV-1 Reverse Transcriptase as a potent target to block HIV replication. (Doctoral Dissertation). Université Montpellier II. Retrieved from http://www.theses.fr/2013MON20238

Chicago Manual of Style (16^th Edition):

Moustapha Abba Moussa, Daouda. “Développement d'inhibiteurs de la dimérisation du complexe de la Reverse Transcription du VIH-1 : Dimerization of HIV-1 Reverse Transcriptase as a potent target to block HIV replication.” 2013. Doctoral Dissertation, Université Montpellier II. Accessed January 20, 2021. http://www.theses.fr/2013MON20238.

MLA Handbook (7^th Edition):

Moustapha Abba Moussa, Daouda. “Développement d'inhibiteurs de la dimérisation du complexe de la Reverse Transcription du VIH-1 : Dimerization of HIV-1 Reverse Transcriptase as a potent target to block HIV replication.” 2013. Web. 20 Jan 2021.

Vancouver:

Moustapha Abba Moussa D. Développement d'inhibiteurs de la dimérisation du complexe de la Reverse Transcription du VIH-1 : Dimerization of HIV-1 Reverse Transcriptase as a potent target to block HIV replication. [Internet] [Doctoral dissertation]. Université Montpellier II; 2013. [cited 2021 Jan 20]. Available from: http://www.theses.fr/2013MON20238.

Council of Science Editors:

Moustapha Abba Moussa D. Développement d'inhibiteurs de la dimérisation du complexe de la Reverse Transcription du VIH-1 : Dimerization of HIV-1 Reverse Transcriptase as a potent target to block HIV replication. [Doctoral Dissertation]. Université Montpellier II; 2013. Available from: http://www.theses.fr/2013MON20238

23. Kanja, Marine. Coévolution dans le gène pol du VIH-1 : un carrefour aux frontières de nouvelles espèces du VIH : Coevolution within HIV-1 pol gene : a crossroads at the borders of new HIV species.

Degree: Docteur es, Aspects moléculaires et cellulaires de la biologie, 2017, Université de Strasbourg

URL: http://www.theses.fr/2017STRAJ077

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L’intégrase (IN) est l’une des enzymes virales assurant la réplication du VIH. La fonctionnalité des protéines qui, comme celles du VIH, ont une variabilité de… (more)

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L’intégrase (IN) est l’une des enzymes virales assurant la réplication du VIH. La fonctionnalité des protéines qui, comme celles du VIH, ont une variabilité de séquence repose sur des résidus non conservés, en plus des acides aminés conservés entre souches, qui ont un rôle important notamment lorsqu'ils font partie de réseaux de coévolution. Ces réseaux peuvent contrecarrer l'effet délétère d'une mutation par l'introduction de mutations compensatoires ailleurs dans la protéine. Ce travail a mis en évidence, par une étude comparative de différentes souches du VIH, des réseaux de coévolution étendus dans l'IN. Un résultat majeur est l'identification d'un nouveau motif assurant de multiples rôles dans le cycle infectieux. Le motif diffère entre les groupes M et O du VIH, mais est strictement conservé au sein de ces deux groupes en dépit d'une certaine flexibilité génétique en culture de cellules. Ceci suggère que ces groupes ont suivi des chemins évolutifs convergents bien que distincts.

Integrase (IN) is one of the viral enzymes ensuring HIV replication. The functionality of proteins, which, like those from HIV, have sequence variability, relies on nonconserved residues, in addition to the conserved amino acids between strains, which have an important role especially when they are part of coevolution networks. These networks can counteract the deleterious effect of a mutation by introducing compensatory mutations elsewhere in the protein. This work has demonstrated, through a comparative study of different strains of HIV, extensive coevolution networks in IN. A major result is the identification of a new motif that provides multiple roles in the infectious cycle. The pattern differs between HIV groups M and O, but is strictly conserved within these two groups despite some genetic flexibility in cell culture. This suggests that these groups followed convergent, although distinct, evolution pathways.

Advisors/Committee Members: Negroni, Matteo (thesis director).

Subjects/Keywords: VIH; Intégrase; Réseaux de coévolution; Fonctionnalité; HIV; Integrase; Coevolution networks; Functionality; 572.8; 616.91

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Kanja, M. (2017). Coévolution dans le gène pol du VIH-1 : un carrefour aux frontières de nouvelles espèces du VIH : Coevolution within HIV-1 pol gene : a crossroads at the borders of new HIV species. (Doctoral Dissertation). Université de Strasbourg. Retrieved from http://www.theses.fr/2017STRAJ077

Chicago Manual of Style (16^th Edition):

Kanja, Marine. “Coévolution dans le gène pol du VIH-1 : un carrefour aux frontières de nouvelles espèces du VIH : Coevolution within HIV-1 pol gene : a crossroads at the borders of new HIV species.” 2017. Doctoral Dissertation, Université de Strasbourg. Accessed January 20, 2021. http://www.theses.fr/2017STRAJ077.

MLA Handbook (7^th Edition):

Kanja, Marine. “Coévolution dans le gène pol du VIH-1 : un carrefour aux frontières de nouvelles espèces du VIH : Coevolution within HIV-1 pol gene : a crossroads at the borders of new HIV species.” 2017. Web. 20 Jan 2021.

Vancouver:

Kanja M. Coévolution dans le gène pol du VIH-1 : un carrefour aux frontières de nouvelles espèces du VIH : Coevolution within HIV-1 pol gene : a crossroads at the borders of new HIV species. [Internet] [Doctoral dissertation]. Université de Strasbourg; 2017. [cited 2021 Jan 20]. Available from: http://www.theses.fr/2017STRAJ077.

Council of Science Editors:

Kanja M. Coévolution dans le gène pol du VIH-1 : un carrefour aux frontières de nouvelles espèces du VIH : Coevolution within HIV-1 pol gene : a crossroads at the borders of new HIV species. [Doctoral Dissertation]. Université de Strasbourg; 2017. Available from: http://www.theses.fr/2017STRAJ077

University of California – Irvine

24. Patterson, Kurt. Transposons: molecular tools for genome investigation.

Degree: Biomedical Sciences, 2016, University of California – Irvine

URL: http://www.escholarship.org/uc/item/6500f1w5

► Transposable elements are DNA sequences capable of moving or copying and reinserting themselves in the genome of a host cell. The Hermes DNA transposon was… (more)

▼ Transposable elements are DNA sequences capable of moving or copying and reinserting themselves in the genome of a host cell. The Hermes DNA transposon was originally found in the housefly Musca domestica. Since its discovery, Hermes has been adapted to multiple eukaryotic species for random mutagenesis or mapping of chromatin structure. The Ty3 retrotransposons of S. cerevisiae is a long terminal repeat (LTR) mobile element of the gypsy–like class. Ty3 is unique among retroelements for its highly specific targeting of RNAP3-transcribed genes for integration. In this dissertation, each of these mobile elements are utilized for different purposes. The Ty3 retrotransposon was used to investigate the relationship between integrase and host factors that direct insertion site selection. Ty3 integration events were quantitatively profiled genome-wide, demonstrating an unexplained bias within an already limited selection of RNAP3 targets. This bias was not defined by the host chromatin environment flanking target sites, and investigation of RNAP3 factors found poor agreement with Ty3 targeting bias. DNA sequence composition and structure of local target sequence were found to regulate integration frequency, in a motif-independent manner. The Hermes DNA transposon was used to establish a functional genomics system for the oleaginous yeast Yarrowia lipolytica, a quickly emerging and valuable microbe with many biotechnology applications. Identification of essential genes provides important information required for genome engineering. Hermes was used to mutagenize a population of Y. lipolytica. To classify essential and non-essential genes, transposon were profiled in surviving mutants by statistically testing under-representation of insertions relative to an expected number derived for each gene. The Y. lipolytica genome was categorized as 20.8 % essential, 71.1 % non-essential and 8.1 % poor essential. Many essential differed from S. cerevisiae, demonstrating the utility of a model obligate aerobe compared to current model yeasts. Pooled mutants were grown for 80 generations in glucose or glycerol, an industrial waste stream, to identify genes contributing to fitness. Glycerol media created a much more competitive environment than glucose. Gene classifications inform future metabolic studies by fine tuning flux analysis and genome scale models, while mutant libraries provide a pipeline for rescreening phenotypes relevant to industrial applications.

Subjects/Keywords: Molecular biology; Biology; Bioinformatics; Hermes DNA Transposon; Integrase; RNAP3; Transposon; transposon profiling; Yarrowia lipolytica

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Patterson, K. (2016). Transposons: molecular tools for genome investigation. (Thesis). University of California – Irvine. Retrieved from http://www.escholarship.org/uc/item/6500f1w5

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Patterson, Kurt. “Transposons: molecular tools for genome investigation.” 2016. Thesis, University of California – Irvine. Accessed January 20, 2021. http://www.escholarship.org/uc/item/6500f1w5.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Patterson, Kurt. “Transposons: molecular tools for genome investigation.” 2016. Web. 20 Jan 2021.

Vancouver:

Patterson K. Transposons: molecular tools for genome investigation. [Internet] [Thesis]. University of California – Irvine; 2016. [cited 2021 Jan 20]. Available from: http://www.escholarship.org/uc/item/6500f1w5.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Patterson K. Transposons: molecular tools for genome investigation. [Thesis]. University of California – Irvine; 2016. Available from: http://www.escholarship.org/uc/item/6500f1w5

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

25. Yajjou, Halima. Études moléculaires et structurales - d’un nouveau mode de dimérisation des intégrases rétrovirales pour développer des modulateurs d’oligomérisation ET - de l’intégrase porcine de PERV-A/C en complexe avec son cofacteur cellulaire humain Brd2 dans un contexte de xénotransplantatio : Molecular and structural studies of a novel dimerization model of retroviral integrases for oligomerization modulators development AND PERV-A/C porcine integrase complexed to its human cellular cofactor Brd2 in a xenotransplantation context.

Degree: Docteur es, Biochimie, 2017, Lyon

URL: http://www.theses.fr/2017LYSE1035

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L'intégrase (IN) est une enzyme essentielle du cycle réplicatif des rétrovirus, qui catalyse l'intégration de l'ADN viral rétrotranscrit dans le génome de la cellule cible.… (more)

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L'intégrase (IN) est une enzyme essentielle du cycle réplicatif des rétrovirus, qui catalyse l'intégration de l'ADN viral rétrotranscrit dans le génome de la cellule cible. Des données structurales, précédemment obtenues par notre équipe, ont conduit à la conception rationnelle de molécules susceptibles de bloquer l'IN sous une forme oligomérique inactive. Des tests d'intégration concertée in vitro ont permis d'étudier leur effet sur l'activité enzymatique de l'IN.Le porc est porteur d'un Gammaretrovirus endogène appelé Porcine Endogenous RetroVirus (PERV), susceptible d'être transmis à l'homme lors d'une xénotransplantation. L'étude structurale de l'IN du virus recombinant PERV-A/C a pour but de mieux comprendre son fonctionnement et de guider le développement rationnel d'inhibiteurs limitant le risque de xénozoonose. J'ai modélisé l'intasome de l'IN de PERV-A/C en complexe avec le raltégravir, un médicament utilisé comme traitement anti-VIH. J'ai ensuite mis au point des protocoles de purification permettant d'étudier le domaine carboxy-terminal (Carboxy Terminal Domain ou CTD) de l'IN de PERV-A/C isolé et en complexe avec le CTD du cofacteur cellulaire humain Brd2. L'enveloppe SAXS de ce complexe a été déterminée. En parallèle, une étude par histone array, réalisée avec le CTD seul de l'IN de PERV-A/C, a révélé un profil de spécificité pour des queues d'histones H2B et H3 portant des modifications post-traductionnelles

Integrase (IN) is an essential enzyme in retroviral replicative cycle, which catalyzes the integration of the viral DNA into the target cell genome. Structural data previously obtained by our team led to rational design of molecules likely to block IN in an inactive oligomeric form. In vitro concerted integration assays made it possible to study their effect on IN enzymatic activity. Pig has an endogenous gammaretrovirus called Porcine Endogenous RetroVirus (PERV) which can be transmitted to humans during xenotransplantation. The aim of the structural study of the recombinant virus PERV-A/C IN is to better understand its mechanism and thus guide the rational design of inhibitors limiting xenozoonosis risk. I modeled the PERV-A/C IN intasome in complex with raltegravir, a drug used for HIV treatment. Then I developed purification protocols to study the isolated and complexed PERV-A/C IN Carboxy-Terminal Domain (CTD) with the human cellular cofactor Brd2. The SAXS envelope of the complex was determined. In parallel, a histone array study, performed with the PERV-A/C IN CTD alone, revealed a specificity profile for modified H2B and H3 histone tails

Advisors/Committee Members: Gouet, Patrice (thesis director), Ronfort, Corinne (thesis director).

Subjects/Keywords: Retrovirus; Intégrase; Dimérisation; Brd2; PERV; Xénotransplantation; Retrovirus; Integrase; Dimerization; Brd2; PERV; Xenotransplantation; 572

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Yajjou, H. (2017). Études moléculaires et structurales - d’un nouveau mode de dimérisation des intégrases rétrovirales pour développer des modulateurs d’oligomérisation ET - de l’intégrase porcine de PERV-A/C en complexe avec son cofacteur cellulaire humain Brd2 dans un contexte de xénotransplantatio : Molecular and structural studies of a novel dimerization model of retroviral integrases for oligomerization modulators development AND PERV-A/C porcine integrase complexed to its human cellular cofactor Brd2 in a xenotransplantation context. (Doctoral Dissertation). Lyon. Retrieved from http://www.theses.fr/2017LYSE1035

Chicago Manual of Style (16^th Edition):

Yajjou, Halima. “Études moléculaires et structurales - d’un nouveau mode de dimérisation des intégrases rétrovirales pour développer des modulateurs d’oligomérisation ET - de l’intégrase porcine de PERV-A/C en complexe avec son cofacteur cellulaire humain Brd2 dans un contexte de xénotransplantatio : Molecular and structural studies of a novel dimerization model of retroviral integrases for oligomerization modulators development AND PERV-A/C porcine integrase complexed to its human cellular cofactor Brd2 in a xenotransplantation context.” 2017. Doctoral Dissertation, Lyon. Accessed January 20, 2021. http://www.theses.fr/2017LYSE1035.

MLA Handbook (7^th Edition):

Yajjou, Halima. “Études moléculaires et structurales - d’un nouveau mode de dimérisation des intégrases rétrovirales pour développer des modulateurs d’oligomérisation ET - de l’intégrase porcine de PERV-A/C en complexe avec son cofacteur cellulaire humain Brd2 dans un contexte de xénotransplantatio : Molecular and structural studies of a novel dimerization model of retroviral integrases for oligomerization modulators development AND PERV-A/C porcine integrase complexed to its human cellular cofactor Brd2 in a xenotransplantation context.” 2017. Web. 20 Jan 2021.

Vancouver:

Yajjou H. Études moléculaires et structurales - d’un nouveau mode de dimérisation des intégrases rétrovirales pour développer des modulateurs d’oligomérisation ET - de l’intégrase porcine de PERV-A/C en complexe avec son cofacteur cellulaire humain Brd2 dans un contexte de xénotransplantatio : Molecular and structural studies of a novel dimerization model of retroviral integrases for oligomerization modulators development AND PERV-A/C porcine integrase complexed to its human cellular cofactor Brd2 in a xenotransplantation context. [Internet] [Doctoral dissertation]. Lyon; 2017. [cited 2021 Jan 20]. Available from: http://www.theses.fr/2017LYSE1035.

Council of Science Editors:

Yajjou H. Études moléculaires et structurales - d’un nouveau mode de dimérisation des intégrases rétrovirales pour développer des modulateurs d’oligomérisation ET - de l’intégrase porcine de PERV-A/C en complexe avec son cofacteur cellulaire humain Brd2 dans un contexte de xénotransplantatio : Molecular and structural studies of a novel dimerization model of retroviral integrases for oligomerization modulators development AND PERV-A/C porcine integrase complexed to its human cellular cofactor Brd2 in a xenotransplantation context. [Doctoral Dissertation]. Lyon; 2017. Available from: http://www.theses.fr/2017LYSE1035

University of Georgia

26. Shearer, Julia Elaine Servatius. In vivo integron integrase (inti1) abundance affects the type and amount of recombination products differentially during the growth cycle.

Degree: 2014, University of Georgia

URL: http://hdl.handle.net/10724/24491

► The integron integrase IntI1 mediates the transfer of antibiotic resistance gene cassettes between plasmid-carried integrons by two mechanisms, integration and excision or the formation and… (more)

▼ The integron integrase IntI1 mediates the transfer of antibiotic resistance gene cassettes between plasmid-carried integrons by two mechanisms, integration and excision or the formation and resolution of cointegrates. Cointegrates can be isolated from cells expressing integrase under the natural promoter Pint, but cassette capture has never been experimentally observed without excess integrase. Historically, integrase activity has been measured after conjugation or transformation of its recombinant products to a recipient cell. We constructed an integron capture vector pICV8 that acquires and donates antibiotic resistance gene cassettes in strains that overexpress IntI1 and detected recombination products in cells by PCR without conjugative transfer of recombinant plasmids. Qualitative PCR revealed that pICV8 readily forms cointegrates in vivo in strains expressing integrase under its natural promoter on a low copy number plasmid, though cassette capture products are not detected without excess integrase. Using dilution PCR, we report the first measurements of the time- dependence of formation of integron intracellular products. Integrase-mediated recombination products were quantified over time using dilution PCR in low and high integrase strains. Only cointegrates were detectable in strains expressing integrase under a natural promoter, and the simple acquisition of gene cassettes could only be seen in strains overexpressing integrase. Recombination products in both the low and high integrase strains increased in late log to early stationary phase. attC x attI recombination has been reported to occur 10 times more frequently than attI x attI crossovers, but, unexpectedly, we detected more attI x attI than attC x attI recombination products in log phase for both strains. However, the high integrase strain showed increased attC recombination in stationary phase, consistent with the earlier observations on integrase crossover preferences. Thus, the intracellular abundance of IntI1 affects the amount and type of recombination events, especially toward the end of log phase.

Subjects/Keywords: Integron; integrase; IntI1; attI; attC; recombination; antibiotic resistance; growth cycle; dilution PCR

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Shearer, J. E. S. (2014). In vivo integron integrase (inti1) abundance affects the type and amount of recombination products differentially during the growth cycle. (Thesis). University of Georgia. Retrieved from http://hdl.handle.net/10724/24491

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Shearer, Julia Elaine Servatius. “In vivo integron integrase (inti1) abundance affects the type and amount of recombination products differentially during the growth cycle.” 2014. Thesis, University of Georgia. Accessed January 20, 2021. http://hdl.handle.net/10724/24491.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Shearer, Julia Elaine Servatius. “In vivo integron integrase (inti1) abundance affects the type and amount of recombination products differentially during the growth cycle.” 2014. Web. 20 Jan 2021.

Vancouver:

Shearer JES. In vivo integron integrase (inti1) abundance affects the type and amount of recombination products differentially during the growth cycle. [Internet] [Thesis]. University of Georgia; 2014. [cited 2021 Jan 20]. Available from: http://hdl.handle.net/10724/24491.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Shearer JES. In vivo integron integrase (inti1) abundance affects the type and amount of recombination products differentially during the growth cycle. [Thesis]. University of Georgia; 2014. Available from: http://hdl.handle.net/10724/24491

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Jawaharlal Nehru University

27. Khandrika, Lakshmipathi. Characterization of the integrase gene of the phage PIS136 and its possible use as a molecular tool;.

Degree: Institute of Microbial Technology, 2005, Jawaharlal Nehru University

URL: http://shodhganga.inflibnet.ac.in/handle/10603/16589

none

Bibliography p.118-135

Advisors/Committee Members: Agrawal, Pushpa.

Subjects/Keywords: integrase gene; phage PIS136; molecular tool

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Khandrika, L. (2005). Characterization of the integrase gene of the phage PIS136 and its possible use as a molecular tool;. (Thesis). Jawaharlal Nehru University. Retrieved from http://shodhganga.inflibnet.ac.in/handle/10603/16589

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Khandrika, Lakshmipathi. “Characterization of the integrase gene of the phage PIS136 and its possible use as a molecular tool;.” 2005. Thesis, Jawaharlal Nehru University. Accessed January 20, 2021. http://shodhganga.inflibnet.ac.in/handle/10603/16589.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Khandrika, Lakshmipathi. “Characterization of the integrase gene of the phage PIS136 and its possible use as a molecular tool;.” 2005. Web. 20 Jan 2021.

Vancouver:

Khandrika L. Characterization of the integrase gene of the phage PIS136 and its possible use as a molecular tool;. [Internet] [Thesis]. Jawaharlal Nehru University; 2005. [cited 2021 Jan 20]. Available from: http://shodhganga.inflibnet.ac.in/handle/10603/16589.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Khandrika L. Characterization of the integrase gene of the phage PIS136 and its possible use as a molecular tool;. [Thesis]. Jawaharlal Nehru University; 2005. Available from: http://shodhganga.inflibnet.ac.in/handle/10603/16589

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Penn State University

28. Konsavage, Wesley Merle. IDENTIFICATION OF RESIDUES WITHIN THE 35-AMINO-ACID SPACING REGION OF ROUS SARCOMA VIRUS INTEGRASE THAT ARE IMPORTANT FOR INTERACTIONS WITH ITS VIRAL AND NONVIRAL DNA SUBSTRATES .

Degree: 2008, Penn State University

URL: https://submit-etda.libraries.psu.edu/catalog/7811

► Retrovirus replication requires insertion of the viral genomic DNA into the DNA of the host. This insertion is mediated by the viral integrase enzyme. A… (more)

▼ Retrovirus replication requires insertion of the viral genomic DNA into the DNA of the host. This insertion is mediated by the viral integrase enzyme. A better understanding of how integrase interacts with these two DNA substrates is important for both the development of antiretroviral drugs and for improved retroviral vectors for gene therapy. Integrase specifically recognizes the viral DNA and removes the terminal nucleotides from the 3' end of each strand (this reaction is referred to as processing). The enzyme then inserts this trimmed DNA nonspecifically into the host DNA (this reaction is referred to as DNA joining). Interestingly, avian integrases are known to nick viral DNA at both the biologically relevant site and one nucleotide away from that site when reactions are done in the presence of manganese. However, mutations at residue 124 of Rous sarcoma virus (RSV) integrase yielded enzymes that are more specific for nicking at the biologically relevant site. One of these mutations, S124D, is markedly enhanced for processing activity, both in terms of specificity and effiency, but is dramatically impaired for DNA joining activity. Additional mutations were constructed to determine what properties of the aspartate substitution result in this activity profile. It was found that both the negative charge, the position of the negative charge, and the structure of the substituted amino acid all contributed to the S124D’s activity profile. Moreover, the S124D protein was found to be impaired for binding to nonviral DNA. All retroviral integrases contain a conserved D,D-35-E motif within the core domain. The three acidic residues are known to be required for enzymatic activity, but the importance of the conserved 35-amino-acid spacing is unknown. Mutations were constructed in a flexible loop within this 35-amino-acid spacing that altered the length of the spacing or the flexibility of the loop. It appears that the flexibility of the loop is more important for interactions with viral DNA than nonviral DNA. Additionally, enzymes with alterations to the spacing maintained enzymatic activity. However, virions containing these mutations were defective for replication, suggesting that the 35-amino-acid spacing is important for virus replication. Together, these data show that the D,D-35-E motif participates in distinct and separable functions for integrase acitivity. Advisors/Committee Members: Michael Katzman, Committee Chair/Co-Chair, David Joseph Spector, Committee Member, John Warren Wills, Committee Member, Leslie Joan Parent, Committee Member, Ira Joseph Ropson, Committee Member.

Subjects/Keywords: Rous Sarcoma Virus; retroviral integrase; integration

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Konsavage, W. M. (2008). IDENTIFICATION OF RESIDUES WITHIN THE 35-AMINO-ACID SPACING REGION OF ROUS SARCOMA VIRUS INTEGRASE THAT ARE IMPORTANT FOR INTERACTIONS WITH ITS VIRAL AND NONVIRAL DNA SUBSTRATES . (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/7811

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Konsavage, Wesley Merle. “IDENTIFICATION OF RESIDUES WITHIN THE 35-AMINO-ACID SPACING REGION OF ROUS SARCOMA VIRUS INTEGRASE THAT ARE IMPORTANT FOR INTERACTIONS WITH ITS VIRAL AND NONVIRAL DNA SUBSTRATES .” 2008. Thesis, Penn State University. Accessed January 20, 2021. https://submit-etda.libraries.psu.edu/catalog/7811.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Konsavage, Wesley Merle. “IDENTIFICATION OF RESIDUES WITHIN THE 35-AMINO-ACID SPACING REGION OF ROUS SARCOMA VIRUS INTEGRASE THAT ARE IMPORTANT FOR INTERACTIONS WITH ITS VIRAL AND NONVIRAL DNA SUBSTRATES .” 2008. Web. 20 Jan 2021.

Vancouver:

Konsavage WM. IDENTIFICATION OF RESIDUES WITHIN THE 35-AMINO-ACID SPACING REGION OF ROUS SARCOMA VIRUS INTEGRASE THAT ARE IMPORTANT FOR INTERACTIONS WITH ITS VIRAL AND NONVIRAL DNA SUBSTRATES . [Internet] [Thesis]. Penn State University; 2008. [cited 2021 Jan 20]. Available from: https://submit-etda.libraries.psu.edu/catalog/7811.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Konsavage WM. IDENTIFICATION OF RESIDUES WITHIN THE 35-AMINO-ACID SPACING REGION OF ROUS SARCOMA VIRUS INTEGRASE THAT ARE IMPORTANT FOR INTERACTIONS WITH ITS VIRAL AND NONVIRAL DNA SUBSTRATES . [Thesis]. Penn State University; 2008. Available from: https://submit-etda.libraries.psu.edu/catalog/7811

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

29. Amadori, Céline. Caractérisation de l’effet des inhibiteurs allostériques de l’interaction IN-LEDGF/p75 (INLAIs) sur la réplication du VIH-1 et du SIV : Characterization of the effect of allosteric inhibitors of the IN-LEDGF/p75 interaction (INLAIs) on the replication of HIV-1 and SIV.

Degree: Docteur es, Biologie cellulaire et moléculaire, 2016, Sorbonne Paris Cité

URL: http://www.theses.fr/2016USPCB100

► Le virus de l’immunodéficience humaine (VIH-1) est l’agent causal de la pandémie du syndrome d’immunodéficience acquise (SIDA). Les rétrovirus ont la capacité de rétro-transcrire leur… (more)

▼ Le virus de l’immunodéficience humaine (VIH-1) est l’agent causal de la pandémie du syndrome d’immunodéficience acquise (SIDA). Les rétrovirus ont la capacité de rétro-transcrire leur génome ARN en ADN afin qu’il soit intégré dans celui de l’hôte. Les traitements antirétroviraux (ART) actuels combinent plusieurs classes d’antirétroviraux (ARV) ciblant majoritairement les enzymes virales nécessaires à la réplication du VIH-1: la reverse transcriptase (RT), la protéase (PR) et l’intégrase (IN). L’émergence et la transmission de virus multirésistants à l’ensemble des ARV illustrent la nécessité de développer de nouveaux mécanismes thérapeutiques. Les inhibiteurs catalytiques d’IN (INSTIs) utilisés dans les ART ciblent le site actif de l’enzyme et empêchent ainsi la réaction de transfert de brin de l’intégration du VIH-1. La protéine cellulaire Lens Epithelium-Derived Growth Factor (LEDGF/p75), liée à la chromatine, est l’un des principaux cofacteurs de IN. En permettant le ciblage de l’intégration dans des régions actives du génome de l’hôte, l’interaction IN-LEDGF joue un rôle crucial pour la réplication effective du VIH-1 ce qui en fait une cible de premier ordre pour de nouvelles thérapies. Au cours de ces dernières années, des inhibiteurs allostériques de l’interaction IN-LEDGF (INLAIs encore appelés LEDGINs ou ALLINIs) ont été développés afin d’inhiber l’étape d’intégration. De manière inattendue, ces molécules exercent de fait une double activité antirétrovirale. En effet les INLAIs ciblent l'intégration mais possèdent également une seconde activité plus efficace sur les étapes tardives de la réplication du VIH-1. Celle-ci se traduit par la production de virions présentant un défaut d’infectivité. Mon projet de thèse, réalisé en partenariat avec la société biopharmaceutique Mutabilis, s’est intéressé à la caractérisation de l’activité antirétrovirale d’une nouvelle classe d’INLAIs selon deux axes: (1) l’approfondissement des mécanismes d’action de ces INLAIs sur les étapes tardives de la réplication du VIH-1 ; (2) l’appréciation de leur spectre d’activité sur la réplication du virus de l’immunodéficience simienne (SIV). J’ai pu montrer que les virions produits en présence d’INLAIs développées par Mutabilis présentent un défaut de transcription inverse lors de l’infection des cellules cibles, qui les rend non infectieux. Ces molécules n’influencent pas les étapes tardives de maturation protéique et d’empaquetage de l’ARN du VIH-1 dans les virions. De façon intéressante, ces virions non infectieux sont efficacement reconnus par un panel d’anticorps neutralisants spécifiques de l’enveloppe virale du VIH-1 et conservent la capacité d’induire une réponse immunitaire T CD4+ de type Th1 dans des cellules de patients infectés. Nous avons également évalué l’effet des INLAIs sur la réplication du SIV. Des expérimentations in vitro ont permis de montrer que certaines INLAIs inhibent efficacement l’interaction IN-LEDGF mais n’induisent pas la multimérisation anormale de IN SIV contrairement à ce que nous observons pour IN… Advisors/Committee Members: Emiliani, Stéphane (thesis director).

Subjects/Keywords: VIH-1; SIV; Integrase; LEDGF; Inhibiteur allostériques; Activité antirétrovirale; Cellular and molecular biology; 616.979

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Amadori, C. (2016). Caractérisation de l’effet des inhibiteurs allostériques de l’interaction IN-LEDGF/p75 (INLAIs) sur la réplication du VIH-1 et du SIV : Characterization of the effect of allosteric inhibitors of the IN-LEDGF/p75 interaction (INLAIs) on the replication of HIV-1 and SIV. (Doctoral Dissertation). Sorbonne Paris Cité. Retrieved from http://www.theses.fr/2016USPCB100

Chicago Manual of Style (16^th Edition):

Amadori, Céline. “Caractérisation de l’effet des inhibiteurs allostériques de l’interaction IN-LEDGF/p75 (INLAIs) sur la réplication du VIH-1 et du SIV : Characterization of the effect of allosteric inhibitors of the IN-LEDGF/p75 interaction (INLAIs) on the replication of HIV-1 and SIV.” 2016. Doctoral Dissertation, Sorbonne Paris Cité. Accessed January 20, 2021. http://www.theses.fr/2016USPCB100.

MLA Handbook (7^th Edition):

Amadori, Céline. “Caractérisation de l’effet des inhibiteurs allostériques de l’interaction IN-LEDGF/p75 (INLAIs) sur la réplication du VIH-1 et du SIV : Characterization of the effect of allosteric inhibitors of the IN-LEDGF/p75 interaction (INLAIs) on the replication of HIV-1 and SIV.” 2016. Web. 20 Jan 2021.

Vancouver:

Amadori C. Caractérisation de l’effet des inhibiteurs allostériques de l’interaction IN-LEDGF/p75 (INLAIs) sur la réplication du VIH-1 et du SIV : Characterization of the effect of allosteric inhibitors of the IN-LEDGF/p75 interaction (INLAIs) on the replication of HIV-1 and SIV. [Internet] [Doctoral dissertation]. Sorbonne Paris Cité; 2016. [cited 2021 Jan 20]. Available from: http://www.theses.fr/2016USPCB100.

Council of Science Editors:

Amadori C. Caractérisation de l’effet des inhibiteurs allostériques de l’interaction IN-LEDGF/p75 (INLAIs) sur la réplication du VIH-1 et du SIV : Characterization of the effect of allosteric inhibitors of the IN-LEDGF/p75 interaction (INLAIs) on the replication of HIV-1 and SIV. [Doctoral Dissertation]. Sorbonne Paris Cité; 2016. Available from: http://www.theses.fr/2016USPCB100

30. Merceron, Romain. Etude moléculaire et structurale d'une intégrase rétrovirale pour le développement de nouveaux antirétroviraux et étude cristallographique d' -galactosidases thermostables issues du microorganisme Geobacillus stearothermophilus : Molecular and structural study of a retroviral integrase for the developemnt of new antiretroviral compounds and structural study of thermostable ɑ-galactosidases from Geobacillus stearothermophilus microorganism.

Degree: Docteur es, Biochimie, 2013, Université Claude Bernard – Lyon I

URL: http://www.theses.fr/2013LYO10189

►

L'intégrase (IN) est une protéine clé du cycle de réplication des rétrovirus et constitue une cible thérapeutique importante. Nous avons découvert par cristallographie aux rayons… (more)

▼

L'intégrase (IN) est une protéine clé du cycle de réplication des rétrovirus et constitue une cible thérapeutique importante. Nous avons découvert par cristallographie aux rayons X, une nouvelle possibilité d'assemblage dimérique du domaine central catalytique de l'intégrase du Rous associated virus type I (RAV-1 IN). Dans le cadre de mon travail de thèse, un protocole de surproduction et de purification d'un mutant du domaine catalytique isolé (H103C) a été optimisé, afin de démontrer l'existence de cet assemblage en solution grâce à un pont disulfure inter-moléculaire. Différentes méthodes ont été mises au point, afin de tester la ca pacité de petites molécules d'intérêt à se lier et à stabiliser ce "nouvel" assemblage. Un protocole de surproduction et de purification de l'IN entière du RAV-1 a également été développé et mis au point. Des études structurales ont été réalisées. Un mutant H103C de la protéine entière a été produit, afin de vérifier la formation de la "nouvelle" interface sur la protéine entière. Le microorganisme Geobacillus stearothermophilus produit deux ɑ-galactosidases, AgaA et AgaB, qui appartiennent à la famille GH36 des glycosides hydrolases. Ces deux isoenzymes partagent 97 % d'identité de séquence, mais ont des activités catalytiques différentes. Les structures cristallines d'AgaA et AgaB ont été résolues ainsi que la structures du mutant AgaA et AgaB ont été résolues ainsi que la structure du mutant AgaA A355E, qui présente des caractéristiques enzymatiques similaires de AgaB. L'analyse de ces trois structures montre que la substitution A355E entraîne un déplacement significatif du tryptophane du sous-site catalytiques -1. Ce mouvement peut expliquer les spécificités catalytiques des deux isoenzymes.

Integrase (IN) is a key protein in the retrovirus life cycle and constitutes an important therapeutic target for the development of antiretroviral compounds. This enzyme is involved in the early phase of theretroviral replication cycle and catalyses the retrotranscribed viral DNA integration into the host cell genome.The teams of BioCrystallography and Retrovirology of Lyon Gerland demonstrated by X ray crystallography, the existence of a new dimeric assembly of the central catalytic domain (CCD) of Rous Associated Virus type 1integrase or RAV 1 IN. As part of my thesis work, a protocol of overproduction and purification of the H103Cisolated catalytic domain mutant was developed to demonstrate the existence of this dimeric assembly insolution stabilized by an inter molecular disulfide bond. Biochemical and biophysical methods were developed to test the ability of small molecules of interest to bind and stabilize this "new" assembly. A protocol ofoverproduction and purification of full length RAV1 integrase was developed. Crystallization trials and SAXSstudies were undertaken. The H103C mutant of the entire protein was produced to verify the formation of the"new" interface on the full length protein.The microorganism Geobacillus stearothermophilus produces two thermostable ɑ-galactosidases…

Advisors/Committee Members: Gouet, Patrice (thesis director), Ronfort, Corinne (thesis director).

Subjects/Keywords: Intégrase; Antirétroviraux; Geobacillus stearothermophilus; Ɑ-galactosidases; Integrase; Antiretroviral compounds; Geobacillus stearothermophilus; Ɑ-galactosidases; 579.2

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Merceron, R. (2013). Etude moléculaire et structurale d'une intégrase rétrovirale pour le développement de nouveaux antirétroviraux et étude cristallographique d' -galactosidases thermostables issues du microorganisme Geobacillus stearothermophilus : Molecular and structural study of a retroviral integrase for the developemnt of new antiretroviral compounds and structural study of thermostable ɑ-galactosidases from Geobacillus stearothermophilus microorganism. (Doctoral Dissertation). Université Claude Bernard – Lyon I. Retrieved from http://www.theses.fr/2013LYO10189

Chicago Manual of Style (16^th Edition):

Merceron, Romain. “Etude moléculaire et structurale d'une intégrase rétrovirale pour le développement de nouveaux antirétroviraux et étude cristallographique d' -galactosidases thermostables issues du microorganisme Geobacillus stearothermophilus : Molecular and structural study of a retroviral integrase for the developemnt of new antiretroviral compounds and structural study of thermostable ɑ-galactosidases from Geobacillus stearothermophilus microorganism.” 2013. Doctoral Dissertation, Université Claude Bernard – Lyon I. Accessed January 20, 2021. http://www.theses.fr/2013LYO10189.

MLA Handbook (7^th Edition):

Merceron, Romain. “Etude moléculaire et structurale d'une intégrase rétrovirale pour le développement de nouveaux antirétroviraux et étude cristallographique d' -galactosidases thermostables issues du microorganisme Geobacillus stearothermophilus : Molecular and structural study of a retroviral integrase for the developemnt of new antiretroviral compounds and structural study of thermostable ɑ-galactosidases from Geobacillus stearothermophilus microorganism.” 2013. Web. 20 Jan 2021.

Vancouver:

Merceron R. Etude moléculaire et structurale d'une intégrase rétrovirale pour le développement de nouveaux antirétroviraux et étude cristallographique d' -galactosidases thermostables issues du microorganisme Geobacillus stearothermophilus : Molecular and structural study of a retroviral integrase for the developemnt of new antiretroviral compounds and structural study of thermostable ɑ-galactosidases from Geobacillus stearothermophilus microorganism. [Internet] [Doctoral dissertation]. Université Claude Bernard – Lyon I; 2013. [cited 2021 Jan 20]. Available from: http://www.theses.fr/2013LYO10189.

Council of Science Editors:

Merceron R. Etude moléculaire et structurale d'une intégrase rétrovirale pour le développement de nouveaux antirétroviraux et étude cristallographique d' -galactosidases thermostables issues du microorganisme Geobacillus stearothermophilus : Molecular and structural study of a retroviral integrase for the developemnt of new antiretroviral compounds and structural study of thermostable ɑ-galactosidases from Geobacillus stearothermophilus microorganism. [Doctoral Dissertation]. Université Claude Bernard – Lyon I; 2013. Available from: http://www.theses.fr/2013LYO10189

Open Access Theses and Dissertations