# The natural killer cell response against mouse cytomegalovirus infection

> **NIH NIH R01** · SLOAN-KETTERING INST CAN RESEARCH · 2024 · $630,290

## Abstract

Project Summary
Natural killer (NK) cells are cytotoxic innate lymphocytes that protect the host against viruses. Newborns and
immunocompromised individuals lacking NK cells and are extremely susceptible to viral infection, including
herpesviruses such as human cytomegalovirus (HCMV). HCMV can be accurately modeled using mouse
cytomegalovirus (MCMV) infection in mice, which represents a robust system for investigating antiviral NK cell
responses. From the previous R01 funding period, my lab has discovered new cellular and molecular
mechanisms underlying NK cell responses against MCMV. This current R01 renewal seeks to understand the
transcriptomic, epigenetic, and metabolic control of the antiviral NK cell response, with studies centering around
a novel role for the transcription factor IRF4. In exciting preliminary data, we find IRF4 is rapidly induced in NK
cells during MCMV infection and plays a critical role in their effector response. For the proposed experiments,
we have generated new transgenic mice with conditional Irf4 ablation. In Aim 1, we will determine how IRF4 is
transcriptionally and epigenetically regulated in activated NK cells, and test how IRF4-deficiency impacts the
function of NK cells against MCMV infection. Aim 2 will identify novel gene targets and binding partners of IRF4
in NK cells by integrating transcriptomic, epigenetic, and proteomic approaches. In Aim 3, we will investigate
whether IRF4 drives antiviral NK cell responses by controlling overall metabolism and mitochondrial health.
Altogether, the studies in this R01 renewal will advance our understanding of the molecular basis by which these
powerful effector cells can mediate protection against pathogen invasion, and establish innovative clinical
paradigms for how NK cells may be harnessed for therapeutic strategies against infectious disease.

## Key facts

- **NIH application ID:** 10764302
- **Project number:** 5R01AI100874-12
- **Recipient organization:** SLOAN-KETTERING INST CAN RESEARCH
- **Principal Investigator:** Joseph Chai-Yuen Sun
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $630,290
- **Award type:** 5
- **Project period:** 2023-01-13 → 2027-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10764302

## Citation

> US National Institutes of Health, RePORTER application 10764302, The natural killer cell response against mouse cytomegalovirus infection (5R01AI100874-12). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10764302. Licensed CC0.

---

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