# Identification of the gene controlling murine retrovirus in YBR mice

> **NIH NIH R21** · UNIVERSITY OF CHICAGO · 2024 · $205,000

## Abstract

Abstract
Differential responses to viral infections are influenced by the genetic makeup of the host. As a result,
sensitivity of humans to viral infections varies considerably, with some individuals withstanding strong viral
pathogens, such as the retrovirus, human immunodeficiency virus (HIV). Studies of inherited resistance to
retroviruses in human populations are enormously complicated, making it difficult to dissect strong antiviral
effector mechanisms that can be taken advantage of when developing therapeutics and vaccines. However,
the variations in the susceptibility of inbred mice to viral infections make the mouse an excellent model for
mapping mechanisms and genes driving mammalian susceptibility and resistance to retroviruses. Exogenous
mouse mammary tumor virus (MMTV) represents a well-studied model of mucosally transmitted retrovirus. The
virus is acquired through the milk in the gut of suckling pups and is passed to the mammary glands by
lymphocytes, where it induces mammary gland tumors after several cycles of re-infection/re-integration.
Susceptibility to exogenous MMTV infection and subsequent mammary tumorigenesis differs drastically among
different mouse strains, ranging from absolute resistance to high susceptibility. Mice from the MMTV-resistant
YBR/Ei (YBR) strain become virus-infected, but do not develop mammary tumors, produce reduced virus titers,
and efficiently eliminate the pathogen in successive generations. In our preliminary studies we found that the
unique mechanism of virus control in YBR mice is unrelated to anti-virus antibodies (Abs), virus-specific CD8+
cytotoxic T lymphocytes, natural killer (NK) cells, and NK T cells, but depends on Thy1+ lymphoid cells.
Moreover, the virus restriction is controlled by a single, dominant locus, which we named attenuation of virus
titers (avt) and have mapped to chromosome 18. Using genetic studies and computational analyses, we will
identify the gene responsible for this remarkable effector mechanism.

## Key facts

- **NIH application ID:** 10894752
- **Project number:** 5R21AI178056-02
- **Recipient organization:** UNIVERSITY OF CHICAGO
- **Principal Investigator:** Tatyana V Golovkina
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $205,000
- **Award type:** 5
- **Project period:** 2023-08-01 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10894752

## Citation

> US National Institutes of Health, RePORTER application 10894752, Identification of the gene controlling murine retrovirus in YBR mice (5R21AI178056-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10894752. Licensed CC0.

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