# Neurovirulent HSV-1 Recombinants for vQTL Analysis

> **NIH NIH R21** · UNIVERSITY OF WISCONSIN-MADISON · 2020 · $229,500

## Abstract

Abstract
Herpes simplex virus type 1 (HSV-1) is a significant human pathogen and is the leading cause of sporadic
encephalitis in the USA. Strains of virus display virulence phenotypes ranging from avirulent to highly
pathogenic. There are indications that the virulence of a given strain of virus is actually determined by the
“constellation” of genes carried by the virus and how they interact with each other; a phenomenon termed
epistasis. Traditional methods for analyzing the function of viral genes are difficult to apply to studying epistatic
interactions in virulence. Recently we described a novel approach, vQTLmap, that has allowed us to identify
contributions of multiple genes to peripheral disease phenotypes. To date we have analyzed four quantitative
phenotypes, blepharitis, stromal keratitis, corneal neovascularization, and weight loss. Surprisingly, there are
distinct differences in the viral genes that appear to be driving each of these phenotypes. In order to carry out
vQTLmap using quantitative measures of neurovirulence, we need to isolate additional neurovirulent
recombinants between the OD4 and CJ994 parental viruses. The goals of this proposal are to generate the
reagents (e.g., neurovirulent recombinants) needed to analyze neurovirulence genes driving HSV-1
encephalitis and identify epistatic interactions and carry out vQTLmap analysis of percent mortality, percent
ataxia, percent head tilt, and percent limb paralysis. At the completion of this project, we will be able to submit
an R01 application to carry out vQTLmap on features such as percent mortality, brain titers of virus,
localization of the infection in the brain, and neuroinvasiveness. A better understanding of how viral genes
work together to promote disease has the potential to identify novel targets that could assist antiviral drug or
vaccine development efforts.

## Key facts

- **NIH application ID:** 9817679
- **Project number:** 5R21AI137280-02
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** Curtis R Brandt
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $229,500
- **Award type:** 5
- **Project period:** 2018-11-07 → 2021-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9817679

## Citation

> US National Institutes of Health, RePORTER application 9817679, Neurovirulent HSV-1 Recombinants for vQTL Analysis (5R21AI137280-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9817679. Licensed CC0.

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