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You searched for +publisher:"Washington University in St. Louis" +contributor:("Anthony R. French"). Showing records 1 – 3 of 3 total matches.

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1. Chapa, Travis. Murine Cytomegalovirus Encodes Proteins that Regulate Viral Late Transcription.

Degree: PhD, Biology and Biomedical Sciences: Molecular Microbiology and Microbial Pathogenesis, 2014, Washington University in St. Louis

Human Cytomegalovirus (HCMV) is a Beta-herpesvirus that causes severe disease in immuno-compromised individuals (including AIDS patients), and is the leading viral cause of congenital birth defects. Murine Cytomegalovirus (MCMV) is the primary surrogate model for HCMV, and resembles the human virus with respect to virion structure, genome organization, gene expression, tissue tropism, and clinical manifestations. In my graduate studies, I discovered the function of two novel MCMV proteins during in vitro infection. I demonstrated that ORF M79 encoded protein pM79, and ORF M92 encoded protein pM92. Both pM79 and pM92 have homologs in HCMV, and I showed that they regulate late viral gene transcription. During infection, a mutant virus for either M79 or M92 accumulated representative viral immediate early gene products, early gene products, and viral DNA sufficiently but had severe reduction in the accumulation of late gene products, thus unable to produce infectious progeny. Analysis of the viral transcriptome via tiled array and quantitative PCR analysis revealed that many late transcripts sensitive to a viral DNA synthesis inhibitor (phosphonoacetic acid) were markedly reduced by pM79 or pM92 mutation. Co-immunoprecipitation and mass spectrometry analysis revealed the interactions between pM92 and pM79, and suggests that they are part of a larger virus transcription complex. A colleague demonstrated that this function was conserved in the HCMV homolog pUL79, and I showed that pM92 expression in trans could complement the growth defect of pUL92 deficient HCMV. My work was the first evidence of this regulatory complex in MCMV. This complex represents a potential new target for therapeutic intervention in CMV disease, and a gateway into studying a largely uncharted viral process that is critical to the viral life cycle. Advisors/Committee Members: Anthony R French.

Subjects/Keywords: cytomegalovirus; late gene; M79; M92; regulation; transcription

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APA (6th Edition):

Chapa, T. (2014). Murine Cytomegalovirus Encodes Proteins that Regulate Viral Late Transcription. (Doctoral Dissertation). Washington University in St. Louis. Retrieved from https://openscholarship.wustl.edu/etd/1289

Chicago Manual of Style (16th Edition):

Chapa, Travis. “Murine Cytomegalovirus Encodes Proteins that Regulate Viral Late Transcription.” 2014. Doctoral Dissertation, Washington University in St. Louis. Accessed December 13, 2019. https://openscholarship.wustl.edu/etd/1289.

MLA Handbook (7th Edition):

Chapa, Travis. “Murine Cytomegalovirus Encodes Proteins that Regulate Viral Late Transcription.” 2014. Web. 13 Dec 2019.

Vancouver:

Chapa T. Murine Cytomegalovirus Encodes Proteins that Regulate Viral Late Transcription. [Internet] [Doctoral dissertation]. Washington University in St. Louis; 2014. [cited 2019 Dec 13]. Available from: https://openscholarship.wustl.edu/etd/1289.

Council of Science Editors:

Chapa T. Murine Cytomegalovirus Encodes Proteins that Regulate Viral Late Transcription. [Doctoral Dissertation]. Washington University in St. Louis; 2014. Available from: https://openscholarship.wustl.edu/etd/1289

2. Fogel, Leslie Abigail. The Resolution Phase of NK Cell Proliferation and IFN Production Following Viral Infection Are Highly Regulated Processes.

Degree: PhD, Biology & Biomedical Sciences (Immunology), 2016, Washington University in St. Louis

In response to MCMV infection, NK cells undergo three distinct phases of proliferation: the non-specific phase mediated by pro-proliferative cytokines; the specific phase mediated by recognition of an MCMV-encoded protein by an NK cell activating receptor, Ly49H; and the resolution phase, whose mechanism is unknown. MCMV infection of RAG mice, which lack all adaptive immune cells, results in prolonged proliferation of NK cells despite similar viral titers compared to wildtype mice. Interestingly, there are different kinetics for Ly49H+ and Ly49H- NK cells. We have identified several additional markers that may distinguish NK cells that have been specifically activated through their receptor from those non-specifically activated by cytokines. Using mice that lack only one or two adaptive lymphocyte populations, we determined that and T cells have a redundant ability to resolve NK cell proliferation. An adoptive transfer system was developed to further probe the characteristics of T cells required for this process. Finally, we have observed a significant decrease in NK cell numbers coincident with the resolution of various NK cell effector functions (IFN production and proliferation), which suggests a role for apoptosis in the resolution of NK cell activation. The resolution of IFN production is associated with increased formation of active caspase 8, which appears to be dependent on signaling through TRAIL-R. Advisors/Committee Members: Anthony R. French, Paul Allen, Marco Colonna, Todd Fehniger, John Russell.

Subjects/Keywords: Apoptosis, Interferon gamma, Murine cytomegalovirus, Natural killer cells, Proliferation; Allergy and Immunology; Immunology and Infectious Disease; Medical Immunology

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

APA (6th Edition):

Fogel, L. A. (2016). The Resolution Phase of NK Cell Proliferation and IFN Production Following Viral Infection Are Highly Regulated Processes. (Doctoral Dissertation). Washington University in St. Louis. Retrieved from https://openscholarship.wustl.edu/art_sci_etds/760

Chicago Manual of Style (16th Edition):

Fogel, Leslie Abigail. “The Resolution Phase of NK Cell Proliferation and IFN Production Following Viral Infection Are Highly Regulated Processes.” 2016. Doctoral Dissertation, Washington University in St. Louis. Accessed December 13, 2019. https://openscholarship.wustl.edu/art_sci_etds/760.

MLA Handbook (7th Edition):

Fogel, Leslie Abigail. “The Resolution Phase of NK Cell Proliferation and IFN Production Following Viral Infection Are Highly Regulated Processes.” 2016. Web. 13 Dec 2019.

Vancouver:

Fogel LA. The Resolution Phase of NK Cell Proliferation and IFN Production Following Viral Infection Are Highly Regulated Processes. [Internet] [Doctoral dissertation]. Washington University in St. Louis; 2016. [cited 2019 Dec 13]. Available from: https://openscholarship.wustl.edu/art_sci_etds/760.

Council of Science Editors:

Fogel LA. The Resolution Phase of NK Cell Proliferation and IFN Production Following Viral Infection Are Highly Regulated Processes. [Doctoral Dissertation]. Washington University in St. Louis; 2016. Available from: https://openscholarship.wustl.edu/art_sci_etds/760

3. Rohatgi, Anjali. Viral and Innate Immune Factors Controlling Disease Susceptibility During Chikungunya Virus Infection.

Degree: PhD, Biology & Biomedical Sciences (Immunology), 2015, Washington University in St. Louis

Chikungunya virus (CHIKV) is a re-emerging pathogen that causes a high fever, painful arthritis and a macular rash. The current outbreak began in Kenya in 2004 and spread throughout the Indian Ocean area and Southeast Asia, infecting millions. During this outbreak, more severe disease manifestations, including lethality, were reported for the first time. To understand one possible reason for this change in severity, we explored the impact of genetic changes in the virus on disease pathogenesis. In addition, we dissected the role of type I interferon (IFN) subtypes in CHIKV infection. From these studies, we have gained important insight into the viral and host factors that contribute to CHIKV pathogenesis. To test if one factor contributing to the increased disease severity is genetic changes in the viral genome we compared the pathogenesis of two strains: the first from Senegal in 1983 (37997) and the second from La Reunion in 2006 (LR2006 OPY1). Neonatal mice infected with LR2006 OPY1 developed prolonged viremia, elevated viral loads in the muscle, hind limb weakness and massive myonecrosis compared to 37997-infected mice. A detailed analysis revealed that the LR2006 OPY1 strain displayed a unique ability to infect myofibers following intradermal infection. This difference in tropism appeared to be due to its ability to access the myofiber niche since both infected myofibers and established similar viral loads when given intramuscularly. Thus, LR2006 OPY1 has an enhanced ability to infect myofibers during a natural infection which contributes to severe muscle damage. Studies to identify the genetic differences responsible for the myofiber phenotype are ongoing. Central to the control of acute CHIKV infection is the type I interferon response which induces a potent anti-viral state and modulates the immune response. To further evaluate the role of IFNs during CHIKV infection, we characterized mice lacking specific IFN subtypes. Mice lacking IFN-kappa displayed a modest increase in lethality compared to wild-type mice, and increases in viral loads late in infection, particularly in the brain. Surprisingly, IFN-kappa-/- were resistant to CHIKV-induced lethality, and had similar viral loads and proinflammatory cytokine induction as wild-type mice, suggesting the mechanism for IFN-kappa; is distinct from other IFN subtypes. Recombinant tools are being developed to further analyze the function of IFN-kappa. Together these data provide important insight into the host factors that control pathogenesis and offer evidence that genetic differences in viral strains that alter tropism can contribute to changes in disease severity. Understanding these factors will aid in the development of future therapeutics that target CHIKV infection. Advisors/Committee Members: Deborah J Lenschow, Jacco Boon, Marco Colonna, Michael S Diamond, Anthony R French, Wayne M Yokoyama.

Subjects/Keywords: Chikungunya, Innate Immunity, Interferons, Myositis; Biology

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

APA (6th Edition):

Rohatgi, A. (2015). Viral and Innate Immune Factors Controlling Disease Susceptibility During Chikungunya Virus Infection. (Doctoral Dissertation). Washington University in St. Louis. Retrieved from https://openscholarship.wustl.edu/art_sci_etds/490

Chicago Manual of Style (16th Edition):

Rohatgi, Anjali. “Viral and Innate Immune Factors Controlling Disease Susceptibility During Chikungunya Virus Infection.” 2015. Doctoral Dissertation, Washington University in St. Louis. Accessed December 13, 2019. https://openscholarship.wustl.edu/art_sci_etds/490.

MLA Handbook (7th Edition):

Rohatgi, Anjali. “Viral and Innate Immune Factors Controlling Disease Susceptibility During Chikungunya Virus Infection.” 2015. Web. 13 Dec 2019.

Vancouver:

Rohatgi A. Viral and Innate Immune Factors Controlling Disease Susceptibility During Chikungunya Virus Infection. [Internet] [Doctoral dissertation]. Washington University in St. Louis; 2015. [cited 2019 Dec 13]. Available from: https://openscholarship.wustl.edu/art_sci_etds/490.

Council of Science Editors:

Rohatgi A. Viral and Innate Immune Factors Controlling Disease Susceptibility During Chikungunya Virus Infection. [Doctoral Dissertation]. Washington University in St. Louis; 2015. Available from: https://openscholarship.wustl.edu/art_sci_etds/490

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