# Metabolic control of neurotropic viral infection

> **NIH NIH R21** · UNIVERSITY OF WASHINGTON · 2020 · $485,375

## Abstract

Project Summary/Abstract- Metabolic regulation of viral encephalitis
 As long-lived cells with limited capacity for self-renewal, neurons employ unique strategies to resist
pathogen infection while limiting immunopathology. We recently described one such pathway, using models
of Zika (ZIKV)and West Nile virus (WNV)-induced encephalitis: We found that these infections lead to up-
regulation of the metabolic enzyme IRG1 and accumulation of its product, the metabolite itaconate, within
infected neurons. Itaconate potently inhibits succinate dehydrogenase, a key component of energetic
metabolism. The resultant alteration in neuronal metabolism limits viral replication within neurons, and was
required for survival to these models of viral encephalitis. Notably, the IRG1/itaconate metabolic axis has
received significant recent attention for its role in limiting inflammatory responses in peripheral
macrophages. As viral encephalitis is also characterized by neuroinflammation, and as IRG1 is upregulated
along with a host cytokines and chemokines within the CNS, we hypothesize that IRG1-mediated itaconate
production alters neuronal metabolism to limit both viral replication and neuroinflammation. Interestingly, our
data indicate that itaconate is both secreted and taken up by cultured cells, leading us to further
hypothesize that itaconate is a diffusible molecule capable of broadly altering viral susceptibility and
metabolism across tissue microenvironments. To test these hypotheses, we will first investigate the
mechanism by which itaconate-mediated metabolic alterations restrict viral replication in neurons. We will
then investigate the anti-inflammatory role of itaconate, assessing both its cell-intrinsic function and its
putative role as a diffusible “metabokine.”

## Key facts

- **NIH application ID:** 9954604
- **Project number:** 1R21NS116256-01
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** Andrew Atwell Oberst
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $485,375
- **Award type:** 1
- **Project period:** 2020-04-01 → 2021-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9954604

## Citation

> US National Institutes of Health, RePORTER application 9954604, Metabolic control of neurotropic viral infection (1R21NS116256-01). Retrieved via AI Analytics 2026-06-12 from https://api.ai-analytics.org/grant/nih/9954604. Licensed CC0.

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