# The natural killer cell response against mouse cytomegalovirus infection

> **NIH NIH R01** · SLOAN-KETTERING INST CAN RESEARCH · 2020 · $532,958

## Abstract

Project Summary
Natural killer (NK) cells constitute an important arm of the host immune system that
detects and eliminates virus-infected cells. Newborns and immunocompromised patients
lack NK cells and are extremely susceptible to viral infection, and in particular, human
cytomegalovirus (HCMV) can cause severe health complications or be life-threatening in
these individuals. Mouse cytomegalovirus (MCMV) is an accurate and robust model for
HCMV infection, and represents a good system to study antiviral NK cell responses.
Using MCMV infection in mice, we have discovered that NK cells possess novel
adaptive immune features such as clonal expansion and long-lived memory. From the
funding in the initial R01 period, our lab has uncovered many of the cellular and
molecular mechanisms underlying NK cell memory. Our long-term goals are to
understand the general biology of NK cells and the molecular basis by which these
powerful effector cells can mediate protection against pathogen invasion. To this end,
we have recently identified a novel role for the transcription factor IRF8 in the NK cell
response against MCMV infection. Based on this exciting preliminary data, our current
R01 renewal proposes to use a newly-generated transgenic mouse where Irf8 is
specifically ablated in NK cells to study the impact of this transcription factor in antiviral
responses. In Aim 1, we will perform epigenetic profiling of activated NK cells to
determine how IRF8-mediated NK cell expansion and effector function are controlled
following MCMV infection. In Aim 2, we will identify the binding partners and gene
targets of IRF8 in antiviral NK cells using proteomic and transcriptomic analyses,
respectively. In Aim 3, we will measure mitochondrial health and metabolism in antiviral
NK cells to investigate the mechanisms behind IRF8-mediated survival of effector and
memory NK cells during the contraction phase following MCMV clearance. Together, the
studies in this R01 renewal will not only advance our understanding of the transcriptional
mechanisms whereby NK cells contribute to host defense during viral infection, but also
establish novel clinical paradigms for how the NK cell compartment may be harnessed
for immunization and therapeutic strategies against infectious disease.

## Key facts

- **NIH application ID:** 9962272
- **Project number:** 5R01AI100874-09
- **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:** 2020
- **Award amount:** $532,958
- **Award type:** 5
- **Project period:** 2012-06-18 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9962272

## Citation

> US National Institutes of Health, RePORTER application 9962272, The natural killer cell response against mouse cytomegalovirus infection (5R01AI100874-09). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9962272. Licensed CC0.

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