# CD4 T cell control of cytomegalovirus

> **NIH NIH R01** · LA JOLLA INSTITUTE FOR IMMUNOLOGY · 2020 · $720,659

## Abstract

Summary
Cytomegalovirus (CMV, a b-herpesvirus) establishes a persistent infection that is endemic in humans and mice.
CMV causes acute clinical disease only if immunity is naïve or compromised, exemplifying how coevolution with
its host over millennia has resulted in a largely non-pathogenic détente. However, this `percolating' infection
imposes a huge footprint on the immune system, especially the T cell memory pool, and growing evidence
suggests this may ultimately be detrimental. Mounting a rapid CD4 T cell response correlates with protection
from CMV-associated disease and reduced viral shedding. Our lab identified the first mouse CMV (MCMV)
epitope-specific CD4 T cells. Of these, one response against the viral M09 protein expands long after systemic
viral infection is controlled, and is critical for resolving the persistent-phase of CMV replication. Our new data
show these `late-rising' M09 cells are unique with regards to their phenotype, effector function and transcriptome
when compared to conventional CD4 T cells that expand early during infection. Additionally, vaccine-induced
late-rising CD4 T cells provide potent protection against CMV challenge. Our overarching hypothesis is that
distinct immune environments during the acute and persistent phases of CMV infection promote the
expansion/differentiation of these late-rising cells that ultimately resolve persistence and promote latency
establishment. We will determine why these cells show such delayed expansion, determine whether they use
unique mechanisms of cytolysis to kill infected cells and resolve persistence and initiate studies to determine
whether similar CD4 T cells exist in CMV infected people. Together this proposal represents a comprehensive
plan using unique viral tools and omics-based approaches to elucidate how newly identified late-rising CD4 T
cells function to resolve persistent CMV replication, a question that has remained largely unaddressed to date.

## Key facts

- **NIH application ID:** 9867622
- **Project number:** 5R01AI139749-02
- **Recipient organization:** LA JOLLA INSTITUTE FOR IMMUNOLOGY
- **Principal Investigator:** CHRISTOPHER A BENEDICT
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $720,659
- **Award type:** 5
- **Project period:** 2019-02-07 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9867622

## Citation

> US National Institutes of Health, RePORTER application 9867622, CD4 T cell control of cytomegalovirus (5R01AI139749-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9867622. Licensed CC0.

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