# HCMV UL4 Regulation of Host Signaling to Control Viral Latency and Reactivation

> **NIH NIH P20** · UNIVERSITY OF NEBRASKA LINCOLN · 2022 · $178,415

## Abstract

PROJECT SUMMARY/ABSTRACT 
Human cytomegalovirus (HCMV) is a prototypical beta-herpesvirus that infects a majority of the world’s 
population. Although most HCMV infections are asymptomatic in healthy individuals, the virus is the leading 
cause of congenital abnormalities following fetal infection and is a significant cause of morbidity and mortality 
during transplant. HCMV is a species-specific virus that establishes a lifelong infection, characterized by 
latency or persistence in CD34+ hematopoietic progenitor cells (HPCs). As with all herpesviruses, HCMV 
latently-infected cells are sequestered from the immune responses and are controlled by the infecting virus. 
HCMV infection of HPCs results in significant effects on cellular hematopoiesis through both direct and 
indirect mechanisms ultimately controlling key cellular pathways involved in stem cell maintenance, 
differentiation, and function. During latency, HCMV expresses a limited number of genes necessary for 
maintenance of the virus, however we still lack an understanding of how many of these gene products 
function. HCMV UL4, a member of the RL11 region, is expressed during latency in primary cells, yet its 
function is unknown. The goal of this project is to determine the role of UL4 in HCMV latency and reactivation. 
Our preliminary data indicates that UL4 is one of the few genes expressed during latency and that it is 
required for latency and/or reactivation. We propose to characterize the functional molecular characteristics 
of UL4 including when and how UL4 is expressed during the viral lifecycle and whether UL4 functions as a 
cellular ligand. In parallel we will determine how UL4 controls HCMV latency and reactivation in HPCs 
including its role in latency establishment, genome maintenance, cellular differentiation, and/or reactivation 
initiation. This project will provide a comprehensive analysis of one of the limited viral latency gene products 
and define how UL4 controls latency. Understanding the processes behind viral latency are key to eradicating 
HCMV and its related pathologies.

## Key facts

- **NIH application ID:** 10488673
- **Project number:** 5P20GM113126-07
- **Recipient organization:** UNIVERSITY OF NEBRASKA LINCOLN
- **Principal Investigator:** Lindsey Beth Crawford
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $178,415
- **Award type:** 5
- **Project period:** 2016-08-15 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10488673

## Citation

> US National Institutes of Health, RePORTER application 10488673, HCMV UL4 Regulation of Host Signaling to Control Viral Latency and Reactivation (5P20GM113126-07). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10488673. Licensed CC0.

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