# Host genetic determinants of diversity in viral-induced neuropathology

> **NIH NIH R01** · TEXAS A&M UNIVERSITY · 2022 · $320,078

## Abstract

PROJECT SUMMARY
Infection by a given virus can cause diverse neurological outcomes and disease pathologies, influenced by the
genetic background of the host. In mice, Theiler's murine encephalomyelitis virus (TMEV) infection leads to
heterogeneous neurological conditions, depending on mouse strain infected. Because of the relevance of
TMEV infection as a tool for studying virally-influenced neurological conditions in humans, there is a critical
need to determine genetic variants and their mechanisms that link TMEV infection to disease outcome. The
long-term goal is to identify and characterize environmental and genetic interactions that contribute to
individual variation in response to viral infection. The objective of this application is to determine how genetic
background influences disease diversity following TMEV infection. The central hypothesis is that genetic
background, as modeled by a new population-based mouse model, will differentially modify susceptibility to
TMEV-induced diseases based upon genetic polymorphisms. The rationale for the proposed research is that a
delineation of the genetic effects underlying the diverse outcomes of TMEV infection is likely to contribute new
insights into the heterogeneity of virally induced human neurological conditions. The hypothesis will be tested
with three specific aims: 1) Evaluate strains of the Collaborative Cross (CC) mouse resource for phenotypic
variation in response to TMEV infection, 2) Evaluate host genome regions for associations with TMEV-induced
phenotypes, and 3) Identify phenotypic modules governed by shared mechanisms. Aim 1 is based on
published and preliminary data showing that TMEV infection causes diverse outcomes depending on the
genetic background of the mouse. Neurological and behavioral phenotyping tests, ELISAs, and histology will
be used to test the hypothesis that the disease pathologies of TMEV infection in different CC mice demonstrate
a hierarchy, to facilitate the identification of groups of mice with similar characteristics that can be linked to
genetically-diverse CC lines. For Aim 2, RNA sequencing and QTL analyses will be used to test the hypothesis
that genomic diversity within CC mice influences variable disease phenotypes. In Aim 3, cytokine analyses,
modularity clustering and candidate gene allele association will be used to test the hypothesis that the
phenotypic diversity among CC strains can be clustered into modules which can be used to identify shared
mechanisms. Our contribution here is expected to be an understanding of the genetic determinants
responsible for phenotypic diversity following TMEV infection using the CC population of mice. The proposed
research is innovative because it uses an experimental mouse model that captures the breadth of genetic
diversity typically found in human populations, thus comprehensively addressing host contributions to virally
influenced neurological conditions. This research is significant because it is expected to co...

## Key facts

- **NIH application ID:** 10297856
- **Project number:** 5R01NS103934-05
- **Recipient organization:** TEXAS A&M UNIVERSITY
- **Principal Investigator:** Candice L. Brinkmeyer-Langford
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $320,078
- **Award type:** 5
- **Project period:** 2017-12-01 → 2024-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10297856

## Citation

> US National Institutes of Health, RePORTER application 10297856, Host genetic determinants of diversity in viral-induced neuropathology (5R01NS103934-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10297856. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*