# Hormonal Regulation of HSV-1 Replication in Neurons

> **NIH NIH R01** · UNIVERSITY OF MARYLAND EASTERN SHORE · 2024 · $363,969

## Abstract

PROJECT SUMMARY/ABSTRACT
HSV–1 infection in neurons remains a mystery. Acute infection in non-neurons is straightforward: the virus
completes its entire life cycle in less than 20 hours with approximately 90 genes encoded. In neurons, the virus
may establish a dormant state of infection, where the robust viral gene expression turns off with only a few
exceptions. Clinically, the HSV–1 reactivation is associated with a variety of neuropathic complications, causing
considerable economic/health burdens.
Our studies suggested that thyroid hormone (TH or T3) played a role in the regulation of HSV–1 replication in
neurons. This hypothesis was supported by our epidemiology data, which shows that patients taking
levothyroxine demonstrated a lower chance of herpes zoster. We presented convincing data indicating that the
TH exerted its effect by binding to its nuclear receptor TR, and the liganded TR occupied the critical HSV–1
regulatory sequences to suppress the viral gene expression and replication. In addition, our publications reveal
for the first time that the latent DRG neurons exhibited much higher sodium channel activity, and that these
neurons with extremely higher excitability are suppressive to viral replication. These observations lead to the
hypothesis that “TH regulates HSV–1 neuronal replication by dual mechanisms: direct binding to the HSV–1 key
regulatory sequences via its nuclear receptor and modulations of neuronal excitability.”
In this proposal, we will first characterize the thyroid hormone-mediated regulation of HSV–1 replication in
neurons during latency and reactivation using computer-guided mutagenesis to generate chimeric virus
by a synthetic genome method. We hypothesize that a critical single nucleotide change within the thyroid
hormone receptor element (TRE) of an important HSV-1 regulatory sequence will disrupt the TH-mediated
epigenetic regulation and control the viral latency and reactivation.
Next, we will determine the impact of thyroid hormone on the functional expression and activity of
voltage-gated sodium channels (VGSC) during HSV–1 latency and reactivation. We will first verify whether
TH increases Na+ channel function through upregulation of growth factors via MAPK/ERK signaling. We will next
use TH or antagonists to monitor the degrees of latency and reactivation. We hypothesize that TH antagonists
will increase HSV–1 reactivation from latently infected mice. To test the hypothesis, we will determine the effects
of TH on the cytokine production in regulating the VGSC activity via modulating signaling pathways or
intracellular trafficking.
Finally, we will respond to the RFA and design a novel enrichment academy to promote DEIA at UMES for
URM students focusing on AAV gene delivery into neurons to investigate HSV–1 latency and other
diseases. UMES has been emphasizing DEIA since its beginning 137 years ago, and we are proud to be
recognized with an NIH R25 Science Education Partnership Award (SEPA) and a five-year...

## Key facts

- **NIH application ID:** 10942534
- **Project number:** 1R01NS138288-01
- **Recipient organization:** UNIVERSITY OF MARYLAND EASTERN SHORE
- **Principal Investigator:** Shaochung Victor Hsia
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $363,969
- **Award type:** 1
- **Project period:** 2024-08-13 → 2029-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10942534

## Citation

> US National Institutes of Health, RePORTER application 10942534, Hormonal Regulation of HSV-1 Replication in Neurons (1R01NS138288-01). Retrieved via AI Analytics 2026-06-12 from https://api.ai-analytics.org/grant/nih/10942534. Licensed CC0.

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