West Nile virus (WNV) is a highly virulent human pathogen of the central nervous system (CNS) and the most common cause of epidemic encephalitis in the United States. There are no vaccines or specific antiviral treatments available for WNV, and accomplishing this requires a more complete understanding of its pathogenesis. In the CNS, myeloid cells, including infiltrating inflammatory monocytes, macrophages, and activated microglia, comprise the majority of the cellular response to WNV encephalitis. Currently, the specific role of each myeloid subset in regulating viral pathogenesis is largely unknown. The primary goal of this proposal is to understand the fundamental biology of myeloid cell populations during WNV infection. To do this, we will 1) establish the mechanisms and significance of WNV-induced monocyte mobilization, 2) define the migration and function of CCR2-expressing monocytes in the WNV-infected CNS, and 3) characterize the neuropathogenic role of CX3CR1-expressing microglia during WNV encephalitis. Detailed knowledge of the specific roles of myeloid cell subsets will provide insights into their fundamental biology and their contribution to host defense. Furthermore, our results will provide the basis for novel intervention strategies targeting myeloid cell subsets in the CNS, when the need for effective treatments is most critical.

Public Health Relevance

This application seeks to understand the cellular response to West Nile virus that involves monocytes, macrophages, and microglia. Understanding the specific roles of these cell subsets as well as the mechanisms by which they migrate during infection will provide insight into their fundamental biology in mediating the host response to acute viral infections in the CNS.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
1R01AI108715-01A1
Application #
8760176
Study Section
Virology - B Study Section (VIRB)
Program Officer
Repik, Patricia M
Project Start
2014-08-05
Project End
2018-07-31
Budget Start
2014-08-05
Budget End
2015-07-31
Support Year
1
Fiscal Year
2014
Total Cost
$352,560
Indirect Cost
$144,560
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