Arthropod-borne viruses (arboviruses) continue to burden human health in spite of impressive advances in public health and medicine. The introduction of these agents into naive ecosystems presents an ongoing challenge. Our ability to predict whether these agents will persist once introduced and/or emerge as significant public health threats is hindered because we know very little about the underlying mechanisms that allow them to adapt to novel and/or changing environments. West Nile virus (WNV) exists in nature as a genetically diverse swarm of competing mutants that differ in varying degrees from a consensus sequence (i.e. as a quasispecies). Our long-term objective is to understand how arbovirus population dynamics are shaped by their transmission cycles, and how these host-virus interactions contribute to arbovirus persistence and emergence. Proposed studies will test the hypothesis that arbovirus quasispecies are associated with mode of transmission and in vivo phenotype. This hypothesis will be tested using WNV, which was recently introduced into North America, as a model system. We will incorporate a research strategy that takes advantage of pre-existing, well genetically characterized WNV populations, our ability to manipulate the WNV genome, and our ability to faithfully model the WNV transmission cycle in the laboratory. This work builds on preliminary studies showing that WNV exists in nature as a quasispecies, and that mosquitoes provide a source of genetic variation to WNV populations while birds limit this variation.
Our specific aims are to (1) determine the impact of mosquito infection and transmission on the WNV quasispecies in mosquitoes, (2) to evaluate the impact of WNV genetic diversity on mosquito vector competence, avian infectivity and viremia, and pathogenesis in mice, and (3) to determine whether more genetically diverse WNV populations are more fit in mosquitoes and birds than less diverse populations. The results of these studies will enhance our basic understanding of the host-virus interactions that allow arboviruses to persist within complex transmission cycles and emerge as health threats.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI067380-04
Application #
7802083
Study Section
Vector Biology Study Section (VB)
Program Officer
Repik, Patricia M
Project Start
2007-05-15
Project End
2012-04-30
Budget Start
2010-05-01
Budget End
2011-04-30
Support Year
4
Fiscal Year
2010
Total Cost
$364,197
Indirect Cost
Name
University of New Mexico
Department
Pathology
Type
Schools of Medicine
DUNS #
868853094
City
Albuquerque
State
NM
Country
United States
Zip Code
87131
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Misencik, Michael J; Grubaugh, Nathan D; Andreadis, Theodore G et al. (2016) Isolation of a Novel Insect-Specific Flavivirus from Culiseta melanura in the Northeastern United States. Vector Borne Zoonotic Dis 16:181-90

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