The emergence and rapid biogeographic expansion of West Nile Virus (WNV;Flaviviridae;Flavivirus) throughout the western hemisphere, as well as the re-emergence of other medically significant viruses, highlight the vulnerability of the United States to both novel and reemerging viral pathogens. To understand how zoonotic viruses evolve following introduction to new habitats, it is necessary to address the selective pressures shaping viral adaptation. Specifically, we must characterize factors important in determining the plasticity (ability of individual genotypes to generalize to many hosts) and adaptability (ability to rapidly produce fitter genotypes) of virus populations interacting with different hosts in order to evaluate the capacity for geographic expansion into new environments. The mechanisms that account for success of a virus in colonization of new environments are poorly characterized. Experimental studies in naturally relevant hosts are generally lacking in virus adaptation studies. These studies are required to provide plausible and relevant mechanistic explanations for adaptability. The proposed research will address this fundamental gap in the state of knowledge through laboratory studies using natural and ecologically relevant mosquito and avian hosts. Studies in the laboratory are the best way to conduct a systematic evaluation of the factors that influence viral adaptation. We have chosen to undertake a comparative study with two flaviviruses, WNV and St. Louis encephalitis virus (SLEV). These two viruses are very closely related antigenically, genetically, and structurally. Nevertheless, their epidemiological patterns in the western hemisphere have differed strongly in recent years. WNV has continued to expand both its host and geographic ranges, producing significant levels of disease in the U.S. every year since its emergence. SLEV, on the other hand, exhibits only periodic outbreaks which remain relatively contained. Whether WNV activity in North America will ultimately mimic that of SLEV remains to be seen, but a comparative study of current genotypes should elucidate genetic correlates which define variable epidemiological patterns. Recent experimental studies in our laboratory have revealed apparent differences in in vitro adaptation between SLEV and WNV. Our extensive BSL-3 laboratory, insectary, and vivarium will allow us to confirm and expand the in vitro results in vivo in natural hosts and further characterize important factors that both constrain and facilitate arbovirus activity in disparate hosts and new environments. These are among the first studies, to the best of our knowledge, using natural vertebrate and mosquito hosts to elucidate mechanisms of viral adaptation.

Public Health Relevance

We have chosen to undertake a comparative study with two flaviviruses, WNV and St. Louis encephalitis virus (SLEV). Recent experimental studies in our laboratory have revealed apparent differences in in vitro adaptation between SLEV and WNV. Our extensive BSL-3 laboratory, insectary, and vivarium will allow us to confirm and expand the in vitro results in vivo in natural hosts and further characterize the important factors that both constrain and facilitate arbovirus activity in various hosts and environments.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI077669-04
Application #
8296658
Study Section
Virology - B Study Section (VIRB)
Program Officer
Repik, Patricia M
Project Start
2009-07-01
Project End
2014-06-30
Budget Start
2012-07-01
Budget End
2013-06-30
Support Year
4
Fiscal Year
2012
Total Cost
$368,474
Indirect Cost
$111,971
Name
Wadsworth Center
Department
Type
DUNS #
153695478
City
Menands
State
NY
Country
United States
Zip Code
12204
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Ciota, Alexander T; Payne, Anne F; Ngo, Kiet A et al. (2014) Consequences of in vitro host shift for St. Louis encephalitis virus. J Gen Virol 95:1281-8
Ciota, Alexander T; Ehrbar, Dylan J; Matacchiero, Amy C et al. (2013) The evolution of virulence of West Nile virus in a mosquito vector: implications for arbovirus adaptation and evolution. BMC Evol Biol 13:71
Van Slyke, Greta A; Ciota, Alexander T; Willsey, Graham G et al. (2012) Point mutations in the West Nile virus (Flaviviridae; Flavivirus) RNA-dependent RNA polymerase alter viral fitness in a host-dependent manner in vitro and in vivo. Virology 427:18-24
Ciota, Alexander T; Ehrbar, Dylan J; Van Slyke, Greta A et al. (2012) Cooperative interactions in the West Nile virus mutant swarm. BMC Evol Biol 12:58
Ciota, Alexander T; Ehrbar, Dylan J; Van Slyke, Greta A et al. (2012) Quantification of intrahost bottlenecks of West Nile virus in Culex pipiens mosquitoes using an artificial mutant swarm. Infect Genet Evol 12:557-64
Ciota, Alexander T; Koch, Evan M; Willsey, Graham G et al. (2011) Temporal and spatial alterations in mutant swarm size of St. Louis encephalitis virus in mosquito hosts. Infect Genet Evol 11:460-8
Ciota, Alexander T; Styer, Linda M; Meola, Mark A et al. (2011) The costs of infection and resistance as determinants of West Nile virus susceptibility in Culex mosquitoes. BMC Ecol 11:23
Ciota, Alexander T; Jia, Yongqing; Payne, Anne F et al. (2009) Experimental passage of St. Louis encephalitis virus in vivo in mosquitoes and chickens reveals evolutionarily significant virus characteristics. PLoS One 4:e7876