# Elucidating the role of Enolase 2 during HCMV infection

> **NIH NIH F31** · UNIVERSITY OF ROCHESTER · 2021 · $46,036

## Abstract

Abstract
Human cytomegalovirus (HCMV) is a leading cause of birth defects and severe illness in immunocompromised
individuals. Understanding how HCMV manipulates cellular metabolism will provide insight into an emerging
host-pathogen interaction that can potentially lead to novel therapeutic targets, an important goal as many
current HCMV therapies have poor bioavailability and elevated toxicity profiles. HCMV induces numerous
metabolic activities and modulates the expression and activity of a variety of host metabolic genes. For many of
these changes, it is unclear how they contribute to successful infection. One gene that we find to be induced
during infection is the neuron-specific Enolase 2. The goal of this proposal is to investigate the role of Enolase 2
during HCMV infection through three specific aims. In the first aim, I will investigate how Enolase 2 expression
contributes to viral infection. My preliminary data show that (i) HCMV induces Enolase 2 during infection, and (ii)
that shRNA-mediated loss of Enolase 2 attenuates viral infection. shRNA- and CRISPR-Cas9- mediated
knockdown/knockout of Enolase 2 will be utilized for all parts of this proposal. The first part of this aim will
investigate the mechanism of this attenuation and where in the viral lifecycle is Enolase 2 required. In the second
part of this aim, I will investigate the specificity of Enolase 2 for viral infection. There are three well defined
isozymes of enolase encoded in the human genome. While these genes are highly conserved, literature has
shown they may have biological differences. I will test the ability of Enolase 1 or Enolase 3 or catalytically dead
Enolase 2 to restore HCMV infection. In my second aim, I will investigate the role of Enolase 2 in HCMV-mediated
metabolic reprogramming. Enolase has not been shown to have a role in regulating glycolysis, yet my preliminary
data show that loss of Enolase 2 ablates glucose consumption during infection. Using LC/MS/MS, I will
investigate changes in metabolic reprogramming that occur during viral infection when Enolase 2 is present or
not. The second part of aim 2 will investigate the requirement of Enolase 2 under different physiological
conditions such as temperature. HCMV infection can cause flu-like symptoms including fever. Therefore,
Enolase 2 may be required over Enolase 1/3 due to its higher stability. In my third aim, I will elucidate the
mechanism behind HCMV induction of Enolase 2. Preliminary data suggest that the UL38 viral protein is required
for the induction of Enolase 2. I will investigate the ability of UL38 to include Enolase 2 expression and determine
the mechanism. Results from this proposal will provide insight into the role of enolase during HCMV infection
and will highlight physiological and biological differences between the enolase isoforms.

## Key facts

- **NIH application ID:** 10141703
- **Project number:** 1F31AI157283-01
- **Recipient organization:** UNIVERSITY OF ROCHESTER
- **Principal Investigator:** Isreal Moreno
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $46,036
- **Award type:** 1
- **Project period:** 2021-09-01 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10141703

## Citation

> US National Institutes of Health, RePORTER application 10141703, Elucidating the role of Enolase 2 during HCMV infection (1F31AI157283-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10141703. Licensed CC0.

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