# Evading innate immunity during human cytomegalovirus latency

> **NIH NIH R01** · UNIVERSITY OF WISCONSIN-MADISON · 2021 · $355,828

## Abstract

Innate immunity senses intracellular pathogens and induces the expression of cellular genes with
antiviral functions. Most if not all viruses encode proteins that inhibit innate immunity during productive, lytic
infections, but the role of innate immunity during viral latency is underappreciated and understudied.
Latency permits human cytomegalovirus (HCMV) to colonize its hosts for their lifetime by avoiding immune
detection and clearance. During latency, the levels of lytic (productive) phase HCMV proteins such as IE1
(Immediate Early 1) are kept extremely low (or completely absent) because the promoter that drives its
expression, the Major Immediate Early Promoter (MIEP) is transcriptionally silenced by heterochromatin.
IE1 is a transcription factor that promotes progression through the viral lytic phase and is a target of
cytotoxic T cells. Therefore, keeping IE1 protein levels low or absent protects latently infected cells from
immune surveillance and restricts reactivation events until the proper stimulus is sensed. We published that
the viral UL138 protein silences IE1 transcription during latency by inhibiting the recruitment of lysine-
specific demethylases (KDMs) to the MIEP that otherwise remove repressive epigenetic histone
methylations to activate transcription. Our preliminary data indicates this occurs, in part, through a
suppression of cellular innate immune pathways. Here we propose to determine how UL138-mediated
evasion of cellular innate immunity contributes to the establishment and maintenance of HCMV latency, with
a particular focus on viral epigenetics and the transcriptional silencing of IE1.

## Key facts

- **NIH application ID:** 10137186
- **Project number:** 5R01AI139180-04
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** ROBERT F KALEJTA
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $355,828
- **Award type:** 5
- **Project period:** 2018-05-02 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10137186

## Citation

> US National Institutes of Health, RePORTER application 10137186, Evading innate immunity during human cytomegalovirus latency (5R01AI139180-04). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10137186. Licensed CC0.

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