# Viral determinants in HSV virulence

> **NIH NIH R01** · UNIVERSITY OF ILLINOIS AT CHICAGO · 2020 · $399,750

## Abstract

Herpes simplex virus (HSV) is the most common cause of infectious blindness
and viral encephalitis in the Western countries. Primary or recurrent infection can lead to
severe disease, yet no licensed vaccine is available. HSV typically initiates infection in
the epithelial cells of mucosa and spreads to sensory neurons where the virus
establishes latency. Reactivation from latency occurs intermittently, which is a lifelong
source for recurrent lesions. Although viral replication in the mucosa or penetration into
the nervous system inflicts damages or inflammation, the disease mechanism is less
clear. As a large DNA virus, HSV evokes antiviral responses through the innate immune
pathways that regulate TANK-binding kinase 1, a key factor required to activate cytokine
expression and autophagy in mammalian cells. Remarkably, while the interferon-
stimulated gene (STING) drives the cytokine response the tripartite motif protein 23
(TRIM23) serves to mediate autophagy. Despite such regulatory control, HSV is able to
compromise host restrictions, which depends on an HSV virulence factor γ134.5. A
central hypothesis of this proposal is that HSV differentially reprograms host immunity,
where a dynamic interplay between viral and cellular factors may determine HSV
spread, virulence and inflammation. Current effort is directed to decipher mechanisms of
HSV pathogenesis. Several aspects of HSV infection will be investigated in a multi-
faceted approach. Accordingly, recombinant HSV will be generated to determine the
nature of HSV interactions with the innate immune factors in epithelial and neuronal
cells. This will dissect elements pertinent to viral interference of the nucleic acid sensing
complexes and autophagy machineries. Furthermore, genetic studies will explore viral
features relevant to ocular replication, spread and neurovirulence. In parallel, gene
expression analysis will assesses ocular and neuoinflammation. Collectively, these
studies will provide an insight into genetic determinants of HSV virulence, which may
inform design of novel antiviral therapeutics or vaccines.

## Key facts

- **NIH application ID:** 10045324
- **Project number:** 1R01AI148148-01A1
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT CHICAGO
- **Principal Investigator:** BIN HE
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $399,750
- **Award type:** 1
- **Project period:** 2020-05-15 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10045324

## Citation

> US National Institutes of Health, RePORTER application 10045324, Viral determinants in HSV virulence (1R01AI148148-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10045324. Licensed CC0.

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