# Identification of the initial cells infected by West Nile virus ex vivo and in vivo

> **NIH NIH R01** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2022 · $557,515

## Abstract

PROJECT SUMMARY:
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-infected individuals, and development of such an arsenal requires a
more complete understanding of its pathogenesis. WNV is primarily transmitted through the bit of an
infected mosquito. Once deposited into the skin, the virus replicates in a local draining lymph node prior to
viremia, which allows the virus to spread to various organs, including the CNS, where neurons are the
major targets of infection. Currently, it is unclear which cells are infected outside of the CNS, but numerous
in vitro studies suggest that myeloid cells, such as monocytes/macrophages, are likely the primary targets.
To begin understanding this in a more physiologically relevant model, we utilized an ex vivo human
lymphoid tissue model, where WNV replicates robustly. We immunophenotyped the WNV-infected cells
and found that a significant proportion were CD4+ T cells. To further validate these findings, we generated
WNV mutant strains that contain cell-specific microRNA (miR) targets (miR-Ts) to restrict WNV replication
in a cell-specific manner. We engineered lymphoid- or myeloid-specific miR-Ts into the genome of WNV
and found that WNV strains unable to replicate in myeloid cells were able to replicate nearly identically to
wild-type WNV strains, while WNV strains incapable of replicating in lymphoid cells were unable to
replicate in this same model. Therefore, we hypothesize that lymphoid cells are essential initial
cellular targets for WNV replication in the periphery. In this application, we seek to identify the cells
that are essential for WNV replication in the human lymphoid tissue ex vivo (Aim 1) as well as in mice
(Aim 2).

## Key facts

- **NIH application ID:** 10595385
- **Project number:** 1R01AI166594-01A1
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** Jean Kyou Lim
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $557,515
- **Award type:** 1
- **Project period:** 2022-09-21 → 2027-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10595385

## Citation

> US National Institutes of Health, RePORTER application 10595385, Identification of the initial cells infected by West Nile virus ex vivo and in vivo (1R01AI166594-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10595385. Licensed CC0.

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