# NATURAL KILLER CELL CONTROL OF MURINE CYTOMEGALOVIRUS INFECTION

> **NIH NIH R01** · WASHINGTON UNIVERSITY · 2020 · $539,174

## Abstract

Abstract
Natural killer (NK) cells kill tumors and infected cells by integrating signals from two functional types of
receptors, activation and inhibitory. In the mouse, many of these receptors belong to the Ly49 family, encoded
by a cluster of highly related genes, discovered by the applicant’s laboratory. The highly polymorphic Ly49
receptors and killer immunoglobulin-like receptors (KIRs) on human NK cells are examples of convergent
evolution. In murine cytomegalovirus (MCMV) infection, the applicant’s laboratory previously showed that
the Ly49H activation receptor is responsible for genetic resistance of C57BL/6 mice to MCMV infections.
Ly49H recognizes a molecule encoded by MCMV, in a manner independent of major histocompatibility
complex class I (MHC-I) alleles. However, studies from other groups suggest that in non-C57BL/6 mice, other
Ly49 activation receptor alleles recognize MCMV-modified MHC-I. Moreover, still other data suggest that
Ly49 inhibitory receptors can also provide protection against MCMV, depending on MHC-I alleles. It has been
challenging to study these issues further due to the complexities of the Ly49 receptors, including their
polymorphism and variegated expression. Nonetheless, these issues are important to understanding the role of
human inhibitory KIRs and their MHC-I ligands that are also paradoxically associated with protection from
viral infection. Here the applicant presents preliminary data that MCMV is controlled by NK cells in a manner
independent of Ly49H but restricted to a specific MHC-I allele. Preliminary data from the applicant’s
laboratory strongly support a role for a Ly49 inhibitory receptor. Thus, the Specific Aims of this proposal are
to: 1) Identify Ly49 responsible for MHC-restricted resistance to MCMV; 2) Determine role of Ly49 responsible
for MHC-restricted resistance; and 3) Determine how MCMV is involved in Ly49-dependent resistance. Thus,
these studies will provide new insight into the function of NK cell inhibitory receptors in infection.

## Key facts

- **NIH application ID:** 9979744
- **Project number:** 5R01AI131680-04
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Wayne M. Yokoyama
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $539,174
- **Award type:** 5
- **Project period:** 2017-09-25 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9979744

## Citation

> US National Institutes of Health, RePORTER application 9979744, NATURAL KILLER CELL CONTROL OF MURINE CYTOMEGALOVIRUS INFECTION (5R01AI131680-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9979744. Licensed CC0.

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