Zika virus (ZIKV) is a mosquito-borne flavivirus that causes severe human disease, including Guillain-Barr syndrome and congenital brain abnormalities such as microcephaly. The ongoing ZIKV epidemic, which continues unabated, has resulted in over 1 million infections in 48 countries and territories in the Americas and was declared a Public Health Emergency of International Concern by the World Health Organization. There are currently no FDA-approved therapeutics or vaccines to combat this devastating pathogen. Further, efforts to develop an effective therapeutic are hampered by the near complete dearth of knowledge regarding ZIKV-host interactions that are critical for virus propagation and/or disease pathogenesis. ZIKV encodes a single open reading frame that is co- and post-translationally processed into 10 proteins. We will use a large-scale proteomics approach to define the sites of phosphorylation on each ZIKV protein and determine their importance for viral propagation. If successful, the proposed studies would significantly advance our basic understanding of ZIKV protein function and uncover candidate host kinase and phosphatase machinery that could be targeted for antiviral development.

Public Health Relevance

Zika virus causes severe human disease, including fetal microcephaly. Currently there are no vaccines or treatments for Zika virus. The goal of this project is to identify phosphorylation sites on Zika virus proteins that are required for Zika virus to grow. This knowledge will significantly advance our understanding of how human proteins control Zika virus protein function and also provide new antiviral targets.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21AI135265-02
Application #
9706721
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Woodson, Sara Elaine
Project Start
2018-06-01
Project End
2021-05-31
Budget Start
2019-06-01
Budget End
2021-05-31
Support Year
2
Fiscal Year
2019
Total Cost
Indirect Cost
Name
University of Vermont & St Agric College
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
066811191
City
Burlington
State
VT
Country
United States
Zip Code
05405