# Metabolic modulation by the HCMV UL38 gene

> **NIH NIH R01** · UNIVERSITY OF ROCHESTER · 2020 · $23,971

## Abstract

Human Cytomegalovirus (HCMV) is a major cause of congenital birth defects and causes severe disease in a
wide variety of immunosuppressed patient populations, including hematological cancer patients and transplant
recipients. We have found that HCMV institutes a pro-viral metabolic program that drives numerous cellular
metabolic activities to support the production of viral progeny. More recently, we find that the HCMV UL38
protein is necessary and sufficient to drive many aspects of HCMV-induced metabolic remodeling, and we
hypothesize that UL38 supports infection through its inhibition of the TSC2 tumor suppressor protein to induce
metabolic modulation. We will test this hypothesis in Aim 1 by elucidating how UL38-TSC2-mediated metabolic
remodeling contributes to HCMV infection. In addition, we find that HCMV-induces the expression of neuronal
enolase 2 (ENO2), which we find is important for robust HCMV infection. We hypothesize that ENO2 induction
is critical for HCMV-mediated metabolic modulation, which we will test in Aim 2. Lastly, we find that both HCMV
infection and UL38 expression sensitizes cells to metabolic perturbations, revealing vulnerabilities that could
potentially be targeted therapeutically. We hypothesize that HCMV infection and UL38 expression induces a
metabolically rigid state that sensitizes cells to metabolic challenges, a hypothesis we will test in Aim 3. The
proposed work will broaden our understanding of an important host pathogen interaction, and given that these
processes are essential for productive infection, the proposed experiments will highlight novel targets for
therapeutic intervention.

## Key facts

- **NIH application ID:** 10199231
- **Project number:** 3R01AI150698-01S1
- **Recipient organization:** UNIVERSITY OF ROCHESTER
- **Principal Investigator:** JOSHUA C MUNGER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $23,971
- **Award type:** 3
- **Project period:** 2020-07-21 → 2021-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10199231

## Citation

> US National Institutes of Health, RePORTER application 10199231, Metabolic modulation by the HCMV UL38 gene (3R01AI150698-01S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10199231. Licensed CC0.

---

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