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Colorado State University

1. Romo, Hannah Elizabeth. Molecular analysis of the genetic determinants that contribute to virulence in lineage 2 West Nile virus.

Degree: 2017, Colorado State University

The ability of arboviruses to impart significant global disease burdens is related to the corresponding capacity of arboviruses to emerge in na├»ve environments or re-emerge in endemic environments. The introduction of West Nile virus (WNV) into North America was marked by rapid spread across the continent, high rates of neuroinvasive disease in humans and horses, and subsequent displacement by newer evolved genotypes. In the last 12 years, an underrepresented lineage of WNV, lineage 2 (L2) has similarly emerged from sub-Saharan Africa into areas of Europe and Russia, causing widespread neurological disease and recurrent enzootic transmission. Given the potential for further geographic spread of L2 WNV and to understand mechanisms that drive emergence events for WNV, I sought to characterize L2 WNV in a comprehensive and comparative manner by investigating potential molecular mechanisms of pathogenesis in mosquitoes, birds, and mice (as models for human disease). A more thorough understanding of the mechanisms that dictate rapid dispersal and endemic maintenance of arboviruses will improve our ability to predict emergence events, increase the effectiveness of surveillance mechanisms, and develop effective intervention strategies. Within lineage 1 (L1) WNV, the role of the NS3-249P amino acid in modulating severe virogenesis in American Crows (AMCRs) has been well established and is predicted to be involved in facilitating the emergent capacity of L1 WNV. The evolution of a proline at the same NS3-249 locus in L2 WNV was initially observed during the first L2 WNV associated outbreak in Europe. However, no bird mortality was observed during the NS3-249P associated L2 WNV outbreak, and the extent of L2 WNV pathogenesis in birds is unclear. In this aim, I examined the viremia titers and mortality profiles of North American AMCRs and house sparrows following infection with African and European L2 WNV strains with and without amino acid mutations at the NS3-249 locus. Our results demonstrate that L2 WNV strains can elicit severe virogenic and fatal outcomes in AMCRs and HOSPs. Additionally, I found that the NS3-249 locus is modulating AMCR viremia titer outcomes, similar to what has been previously observed for the NS3-249 locus in L1 WNV strains. I also demonstrated the 3' UTR of NS10 reduces viremia titers of AMCRs at later time points. The vast majority of our understanding regarding the vector competence of Culex mosquitoes for WNV originates from studies performed with L1 WNV strains, and as such, little information is available regarding the competency of Culex mosquitoes for L2 WNV. To remediate this, I assessed the vector competence phenotypes of two different North American Culex mosquito species for multiple L2 WNV strains. Our results demonstrate that Culex pipiens and Culex quinquefasciatus mosquitoes can effectively transmit L2 WNV. I also identified a L2 strain harboring an NS3-249P mutation (NS10) that limited infection to the midgut of Culex pipiens mosquitoes. The competence of North American Culex… Advisors/Committee Members: Ebel, Greg (advisor), Brault, Aaron (advisor), Blair, Carol (committee member), Bowen, Richard (committee member), Huyvaert, Kate (committee member).

Subjects/Keywords: West Nile virus; Lineage 2

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

APA (6th Edition):

Romo, H. E. (2017). Molecular analysis of the genetic determinants that contribute to virulence in lineage 2 West Nile virus. (Thesis). Colorado State University. Retrieved from http://hdl.handle.net/10217/181331

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

Chicago Manual of Style (16th Edition):

Romo, Hannah Elizabeth. “Molecular analysis of the genetic determinants that contribute to virulence in lineage 2 West Nile virus.” 2017. Thesis, Colorado State University. Accessed August 19, 2017. http://hdl.handle.net/10217/181331.

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

MLA Handbook (7th Edition):

Romo, Hannah Elizabeth. “Molecular analysis of the genetic determinants that contribute to virulence in lineage 2 West Nile virus.” 2017. Web. 19 Aug 2017.

Vancouver:

Romo HE. Molecular analysis of the genetic determinants that contribute to virulence in lineage 2 West Nile virus. [Internet] [Thesis]. Colorado State University; 2017. [cited 2017 Aug 19]. Available from: http://hdl.handle.net/10217/181331.

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

Council of Science Editors:

Romo HE. Molecular analysis of the genetic determinants that contribute to virulence in lineage 2 West Nile virus. [Thesis]. Colorado State University; 2017. Available from: http://hdl.handle.net/10217/181331

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

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