# EPITRANSCRIPTOMIC REGULATION OF CYTOMEGALOVIRUS INFECTION

> **NIH NIH R01** · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · 2021 · $562,370

## Abstract

7. PROJECT SUMMARY / ABSTRACT
Chemical modification of mRNA provides a powerful means to dynamically alter gene expression in eukaryotes
via epitranscriptomic changes. In particular, methylation of adenosine at the N6 position (m6A) constitutes the
most widespread internal base modification to mRNA. Modification of mRNA by m6A influences numerous
biological processes including development, differentiation, reprogramming, circadian rhythm, cell cycle,
disease pathogenesis, and stress responses including virus infection. Significantly, virus-encoded mRNAs are
also chemically modified by m6A, and a role for m6A in Human Cytomegalovirus (HCMV) infection biology is
emerging. As a canonical TORCH (T. gondii, other, rubella virus, HCMV, HSV) pathogen, primary HCMV
infection during pregnancy remains the leading viral cause of birth defects. While HCMV infection causes mild
if any maternal morbidity and is predominately asymptomatic in healthy individuals, it results in life-threatening
disease among the immunocompromised, including solid-organ or stem cell transplant recipients, and is a
significant source of congenital morbidity and mortality among newborn infants in the developed world.
Addressing HCMV congenital infection remains a serious unmet medical need as there is no HCMV vaccine to
prevent primary infection during pregnancy and no current treatment to prevent transmission from mother to
fetus. Our long-term objective is to understand how the chemical modification of host and/or viral RNA
by m6A impacts reproduction of HCMV, a common infection that remains the leading viral cause of
congenital abnormalities. Preliminary results demonstrate that cellular m6A methyltransferase subunits
METTL3/14, the m6A demethylase ALKBH5, and m6A recognition proteins regulate HCMV reproduction and
responses to double strand DNA (dsDNA) in uninfected cells. This is achieved in part through changes in
interferon b gene (IFNB1) expression. These findings establish that m6A RNA modification enzymes regulate
cellular responses to HCMV and dsDNA sensing, which shapes host immunity and contributes to autoimmune
disease. It further suggests that m6A epitranscriptomic changes play a fundamental role in cell-intrinsic innate
immune responses to the TORCH pathogen HCMV. Based upon our preliminary results, we hypothesize that
HCMV reproduction is differentially controlled by the host m6A modification machinery. Here, this hypothesis
will be tested in three specific aims designed to: (i) identify how the host m6A modification machinery is
regulated in response to HCMV infection; (ii) determine how cellular m6A modification enzymes regulate IFNB1
mRNA accumulation in HCMV-infected cells; and (iii) identify how HCMV gene expression is impacted by
differential m6A modification. The project is significant because it investigates how epitranscriptomic changes
impact HCMV reproduction and innate immunity. Understanding how HCMV infection is regulated by
epitranscriptomic RNA modif...

## Key facts

- **NIH application ID:** 10114213
- **Project number:** 5R01AI152543-02
- **Recipient organization:** NEW YORK UNIVERSITY SCHOOL OF MEDICINE
- **Principal Investigator:** Daniel Pearce Depledge
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $562,370
- **Award type:** 5
- **Project period:** 2020-03-01 → 2025-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10114213

## Citation

> US National Institutes of Health, RePORTER application 10114213, EPITRANSCRIPTOMIC REGULATION OF CYTOMEGALOVIRUS INFECTION (5R01AI152543-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10114213. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*