# Viral manipulation of neuronal microRNAs to maintain trophic support and HSV latency

> **NIH NIH R21** · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · 2020 · $207,979

## Abstract

Herpes simplex viruses (HSV-1 and HSV-2) are widespread viral pathogens that persist in the human population
by establishing latency in sensory and sympathetic ganglia after ocular, labial or genital infection, but can also
reactivate to produce different patterns and frequencies of recurrent disease. Latency is maintained through
epigenetic mechanisms that are dependent on continuous signaling initiated by the binding of neurotrophic
factors such as nerve growth factor (NGF) or glial cell line-derived neurotrophic factor (GDNF) to cognate
receptors. Recent studies have shown that signaling via GDNF is critical to maintain both HSV-1 and HSV-2
latency in cultured murine sensory and sympathetic neurons. The as yet poorly understood virus-host
relationship includes changes in the expression of neuronal microRNAs, short non-coding RNAs that fine tune
mRNA translation. Profiling studies in cultured rat embryonic sympathetic neurons showed that HSV-1 infection
can selectively increase the levels of three closely-related and evolutionarily-conserved microRNAs (miR-183,
miR-96 and miR-182) encoded by a single gene locus known collectively as miR183C. Induction occurs at the
level of transcription of the precursor RNA and is mediated by the viral E3 ligase ICP0. Known mRNA targets for
miR183C encode a variety of proteins that either protect cells against physiological and genomic stresses or
help maintain cell type identity and at least in dopaminergic neurons, miR183C can mimic the trophic action of
GDNF. In this project we will test the innovative hypothesis that viral upregulation of miR-183C helps to buffer
the latent reservoir against fluctuations in GDNF signaling. To do this we will first ask whether the miR-183C
locus is responsive to HSV in cultured prenatal and adult murine sensory and sympathetic ganglia (Aim 1). We
will also ask if this is a shared property of HSV-2, which encodes an ICP0 ortholog (Aim 2). Finally, we will ask
using gene knockouts and overexpression whether induction of miR183C can compensate for GDNF in
maintaining HSV-1 latency in adult sympathetic neurons and HSV-2 latency in adult sensory neurons (Aim 3).
Armed with a better understanding of the virus-host interplay in different neuronal types we hope to identify key
regulatory nodes as targets for innovative therapeutic strategies to control or eliminate reactivation.

## Key facts

- **NIH application ID:** 9939455
- **Project number:** 5R21AI147163-02
- **Recipient organization:** NEW YORK UNIVERSITY SCHOOL OF MEDICINE
- **Principal Investigator:** ANGUS C WILSON
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $207,979
- **Award type:** 5
- **Project period:** 2019-06-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9939455

## Citation

> US National Institutes of Health, RePORTER application 9939455, Viral manipulation of neuronal microRNAs to maintain trophic support and HSV latency (5R21AI147163-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9939455. Licensed CC0.

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