# "Survivor" neurons drive persistent inflammation following West Nile virus infection

> **NIH NIH R21** · UNIVERSITY OF WASHINGTON · 2024 · $220,625

## Abstract

Project Summary/Abstract- “Survivor” neurons drive persistent inflammation following West Nile
virus infection
 West Nile virus (WNV) is mosquito-borne flavivirus that can infect neurons of the central nervous
system. Both human patients murine model organisms that survive neuroinvasive WNV display learning,
memory and motor sequelae that persist long after the virus is cleared. While these sequelae have been
associated with persistent inflammation within the CNS, the source of this inflammation has remained
obscure. Previous studies by our group and others have revealed that neurons are remarkably resistant to
programmed cell death in response to multiple stressors, including viral infection. This observation led us to
hypothesize that neurons that are infected with WNV but survive and clear infection—“survivor” neurons—
sustain virus-induced changes that drive long-term inflammation and CNS disfunction. We sought to test
this idea by creating a recombinant clone of WNV that expresses Cre recombinase, then using this virus to
mark “survivor” neurons in the brains of WNV-infected mice. Spatial transcriptomic analysis of these cells
revealed that “survivor” neurons maintain a robust inflammatory signature weeks after viral infection is
cleared. Strikingly, this signature is absent in adjacent, WNV-naïve neurons within the same tissues,
supporting the idea that “survivor” neurons are drivers of persistent CNS inflammation. The goal of the work
proposed here is to use this newly-developed model to first understand the changes to “survivor” neurons
that drive persistent inflammation, and second to assess the consequences of this inflammatory response
on the function of these neurons, on nearby cells and on organismal learning and memory. We suggest that
the use of these new models and emerging technologies will provide important insight into CNS disfunction
caused by WNV infection. We further suggest that this insight may be applicable to long-term virus-induced
inflammatory dysfunction in other settings.

## Key facts

- **NIH application ID:** 10843931
- **Project number:** 5R21AI178512-02
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** Andrew Atwell Oberst
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $220,625
- **Award type:** 5
- **Project period:** 2023-05-18 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10843931

## Citation

> US National Institutes of Health, RePORTER application 10843931, "Survivor" neurons drive persistent inflammation following West Nile virus infection (5R21AI178512-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10843931. Licensed CC0.

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