# The role of TRAIL in immune control of cytomegalovirus

> **NIH NIH R01** · LA JOLLA INSTITUTE FOR IMMUNOLOGY · 2021 · $549,000

## 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. The
nature of this détente is dependent upon the many strategies that CMV uses to subvert detection by
the immune system. TNF-related cytokines are key regulators of antiviral defenses, and we have
shown that both mouse and human CMV (MCMV and HCMV) inhibit expression of the TNF-related
apoptosis inducing ligand death-receptors (TRAIL-DR) via the M166 and UL141 viral proteins,
respectively. Viral mutants lacking these proteins are highly sensitive to control by TRAIL-expressing
innate immune cells during the early-phase of CMV infection. In contrast, if MCMV is unable to restrict
TRAIL-DR signaling via M166, the duration of persistent replication is dramatically longer. This is likely
due to an altered CD4 T cell response that is unable to resolve persistence within the normal time
frame. Together, our past and new results place the TRAIL signaling system at a critical apex in
regulating various phases of the immune response to persistent virus infection. This proposal will reveal
the how this TNF-family cytokine regulates antiviral immune defenses, and will help to define their
broader importance in regulating inflammation and cell death.

## Key facts

- **NIH application ID:** 10180877
- **Project number:** 5R01AI101423-08
- **Recipient organization:** LA JOLLA INSTITUTE FOR IMMUNOLOGY
- **Principal Investigator:** CHRISTOPHER A BENEDICT
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $549,000
- **Award type:** 5
- **Project period:** 2013-01-10 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10180877

## Citation

> US National Institutes of Health, RePORTER application 10180877, The role of TRAIL in immune control of cytomegalovirus (5R01AI101423-08). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10180877. Licensed CC0.

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