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.
| Rückert, Claudia; Ebel, Gregory D (2018) How Do Virus-Mosquito Interactions Lead to Viral Emergence? Trends Parasitol 34:310-321 |
| Weger-Lucarelli, James; Garcia, Selene M; Rückert, Claudia et al. (2018) Using barcoded Zika virus to assess virus population structure in vitro and in Aedes aegypti mosquitoes. Virology 521:138-148 |
| Magalhaes, Tereza; Foy, Brian D; Marques, Ernesto T A et al. (2018) Mosquito-borne and sexual transmission of Zika virus: Recent developments and future directions. Virus Res 254:1-9 |
| Rossi, Shannan L; Ebel, Gregory D; Shan, Chao et al. (2018) Did Zika Virus Mutate to Cause Severe Outbreaks? Trends Microbiol 26:877-885 |
| Ebel, Gregory D (2017) Promiscuous viruses-how do viruses survive multiple unrelated hosts? Curr Opin Virol 23:125-129 |
| Rückert, Claudia; Weger-Lucarelli, James; Garcia-Luna, Selene M et al. (2017) Impact of simultaneous exposure to arboviruses on infection and transmission by Aedes aegypti mosquitoes. Nat Commun 8:15412 |
| Grubaugh, Nathan D; Fauver, Joseph R; Rückert, Claudia et al. (2017) Mosquitoes Transmit Unique West Nile Virus Populations during Each Feeding Episode. Cell Rep 19:709-718 |
| Weger-Lucarelli, James; Duggal, Nisha K; Brault, Aaron C et al. (2017) Rescue and Characterization of Recombinant Virus from a New World Zika Virus Infectious Clone. J Vis Exp : |
| Chotiwan, Nunya; Brewster, Connie D; Magalhaes, Tereza et al. (2017) Rapid and specific detection of Asian- and African-lineage Zika viruses. Sci Transl Med 9: |
| Weger-Lucarelli, James; Duggal, Nisha K; Bullard-Feibelman, Kristen et al. (2017) Development and Characterization of Recombinant Virus Generated from a New World Zika Virus Infectious Clone. J Virol 91: |
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