Zika virus (ZIKV) has recently emerged in the Western Hemisphere, causing a massive, currently ongoing outbreak in South America. ZIKV appears to be neurotropic, with microcephaly and other fetal brain defects being among the most serious outcome of infection. Currently, there are no vaccines or specific antiviral treatments for ZIKV; therefore understanding its pathogenesis in humans is a high priority. ZIKV is phylogenetically related to other flaviviruses, such as dengue virus (DENV) and West Nile virus (WNV). It has recently been proposed that the presence of antibodies against DENV can enhance ZIKV infection through a phenomenon known as antibody-dependent enhancement (ADE). In the continental United States, DENV does not currently circulate; however, WNV has been circulating in the US for over 15 years, causing annual outbreaks of infection. Thus, we hypothesize that antibodies against WNV enhance ZIKV infection. To test this hypothesis, we will 1) determine and characterize the cross reactivity of WNV antibodies with ZIKV, and 2) evaluate the antibody-dependent enhancement in vitro and ex vivo. Our studies will provide much needed insight into understanding how prior infection with WNV could enhance susceptibility to ZIKV.

Public Health Relevance

Infection with Zika virus (ZIKV) may be enhanced by the pre-existence of antibodies against related flaviviruses. In the United States, the primary circulating flavivirus is West Nile virus (WNV). In this application, we will test the hypothesis that infection with WNV is a risk factor for ZIKV infection.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21AI130299-02
Application #
9419290
Study Section
Special Emphasis Panel (ZAI1)
Program Officer
Challberg, Mark D
Project Start
2017-02-01
Project End
2019-01-31
Budget Start
2018-02-01
Budget End
2019-01-31
Support Year
2
Fiscal Year
2018
Total Cost
Indirect Cost
Name
Icahn School of Medicine at Mount Sinai
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
078861598
City
New York
State
NY
Country
United States
Zip Code
10029
Bardina, Susana V; Bunduc, Paul; Tripathi, Shashank et al. (2017) Enhancement of Zika virus pathogenesis by preexisting antiflavivirus immunity. Science 356:175-180