Date of Award

1-1-2012

Language

English

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

College/School/Department

Department of Biological Sciences

Content Description

1 online resource (v, 132 pages) : illustrations

Dissertation/Thesis Chair

Laura D Kramer

Committee Members

Kurt McKean, Thomas Caraco, Paul Turner

Keywords

adaptation, arbovirus, evolution, mosquito, St. louis encephalitis virus, West Nile virus, Arboviruses, Saint Louis encephalitis, Arthropod vectors, Host-virus relationships, Virus-vector relationships, Virology

Subject Categories

Biology | Evolution | Virology

Abstract

Arthropod-borne viruses (arboviruses), which are predominately mosquito-borne and almost exclusively RNA viruses, are maintained in nature in complex transmission cycles involving blood sucking invertebrates and vertebrate hosts. Although over 120 arboviruses are human pathogens responsible for causing a significant and expanding global health burden, a detailed understanding of the complex interactions between these pathogens and their hosts, particularly invertebrate hosts, is lacking. Defining these interactions is necessary if we are to understand the selective pressures and, therefore, evolutionary, adaptive, and epidemiological potential of arboviruses. This requires experimental infection and evolution studies, particularly in vivo, with natural hosts. The results presented here, with West Nile virus (WNV) and St. Louis encephalitis virus (SLEV; Flaviviridae: Flavivirus), are a compilation of such studies. WNV is the most prevalent arboviral pathogen in the U.S. and the most geographically distributed arbovirus in the world. SLEV is a close relative of WNV, with genetic, antigenic, and ecological similarities, yet both geographic range and levels of activity of SLEV are much more limited than WNV. Despite the evolutionary potential of these RNA viruses, arboviruses including WNV and SLEV have experienced only limited consensus level change. This relative evolutionary stasis has been attributed primarily to the requirement for host cycling, yet previous results demonstrate differential selective pressures may be overstated and results presented here demonstrate that evolutionary constraint may also result from interseasonal and intrahost bottlenecks, cooperative interactions in the viral swarm, and virulence in mosquito vectors. In addition, these studies expand on previous work demonstrating that a complete characterization of the mutant swarm, both its breadth and composition, is required if we are to fully evaluate genetic change and its phenotypic consequences. Lastly, these results demonstrate the specificity and complexity of vector-virus interactions and the need to evaluate individual systems independently. Taken together, these studies expand our knowledge of the complex forces shaping arbovirus evolution and adaptation and establish a baseline for future mechanistic studies.

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