This proposal is for a new R21, Predicting genetic determinants of Zika virus emergence. This project aims to take a proactive approach to assessing how Zika may adapt to American vectors. Ultimately, this research will contribute to an expanding body of data and knowledge in the PI?s lab regarding the impact of specific, ecologically relevant vectors and hosts on arbovirus fitness determinants and population genetics. In particular, in this project we will determine how infection of Ae. aegypti, Ae. albopictus and Cx. quinquefasciatus influence ZIKV genetics. We will also assess the role of ambient temperature in shaping virus populations.
Aim 1 focuses on characterizing vector competence of mosquito strains that originate from the Americas for the Asian lineage of ZIKV (i.e. the strain currently circulating in South America). We will then determine how the virus population changes as it passes through important tissue/compartments within each mosquito, including midguts, hemolymph, salivary glands and saliva. This aspect of the proposal is based on our ongoing work with West Nile virus and published literature on Chikungunya virus.
The second aim i s to assess how temperature influences virus mutational diversity during mosquito infection. This is a frequently asked, but never adequately answered question. Together, these aims will permit us to draw linkages across virus-vector systems and to provide predictions regarding likely adaptive mutations to the ZIKV genome that may permit more rapid spread in the Americas. The proposed research leverages extensive experience in virus-vector interactions, NGS and computational biology and a large amount of preliminary data on the WNV-Culex system.

Public Health Relevance

In this project we will assess the likely evolutionary trajectory of Zika virus, an emerging arthropod-borne virus in the genus Flavivirus during transmission by American strains of the vector mosquitoes Aedes aegypti and Ae. albopictus. Specifically we will determine how different mosquitoes and temperatures impact virus genetic diversity within hosts. If successful this project could have a major impact on the field by contributing to a new proactive approach to assessing the conditions that may favor arbovirus emergence.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21AI125996-02
Application #
9284379
Study Section
Vector Biology Study Section (VB)
Program Officer
Costero-Saint Denis, Adriana
Project Start
2016-06-06
Project End
2018-05-31
Budget Start
2017-06-01
Budget End
2018-05-31
Support Year
2
Fiscal Year
2017
Total Cost
$227,875
Indirect Cost
$77,875
Name
Colorado State University-Fort Collins
Department
Microbiology/Immun/Virology
Type
Schools of Veterinary Medicine
DUNS #
785979618
City
Fort Collins
State
CO
Country
United States
Zip Code
80523
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
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
Ebel, Gregory D (2017) Promiscuous viruses-how do viruses survive multiple unrelated hosts? Curr Opin Virol 23:125-129
Weger-Lucarelli, James; Rückert, Claudia; Chotiwan, Nunya et al. (2016) Vector Competence of American Mosquitoes for Three Strains of Zika Virus. PLoS Negl Trop Dis 10:e0005101