# Analysis of the mechanism of HCMV cytoplasmic envelopment

> **NIH NIH R01** · PENNSYLVANIA STATE UNIV HERSHEY MED CTR · 2020 · $375,813

## Abstract

Project Summary
 Although largely asymptomatic, human cytomegalovirus (HCMV) can cause severe and even fatal
disease in a subset of susceptible individuals. While great progress has been made in understanding essential
stages of HCMV replication, a detailed description of many of these processes is lacking. Of particular interest
in this proposal is cytoplasmic envelopment. To provide a molecular description of the events associated with
cytoplasmic envelopment, it is important to identify the factors involved, both viral and cellular. Previous work
has identified UL71 as an envelopment factor that potentially mediates membrane scission, as viruses lacking
UL71 are trapped at various stages of budding. It is not known whether UL71 is sufficient itself for promoting
scission or if it requires other viral and/or cellular factors. Many viruses utilize cellular machinery known as the
endosomal sorting complexes required for transport (ESCRTs) as part of the envelopment process. While
HCMV does not require the early ESCRT-I complex, it does require the late ESCRT Vps4. The role of the
ESCRT-III complex, which is the major driver of membrane deformation and scission promoter, has not yet
been investigated. Understanding the role, if any, for ESCRT-III during infection is essential for providing a
detailed description of cytoplasmic envelopment. We hypothesize that UL71 recruits ESCRT-III and Vps4 to
mediate scission of budding HCMV capsids. In support of this hypothesis, an interaction between UL71 and
Vps4 has been reported. The experiments in this proposal will investigate if ESCRT-III subunits are required
for HCMV replication, and if so at what stage. They will investigate the relationship, if any, between UL71 and
ESCRT-III and define a function for the UL71-Vps4 interaction, as well as identify regions on UL71 important
for function. These studies will further our understanding of the contribution of cellular factors to HCMV
infection and potentially identify novel ways in which viral replication can be targeted. Taken together, these
studies will lay the foundation for a mechanistic understanding of HCMV cytoplasmic envelopment.

## Key facts

- **NIH application ID:** 9952297
- **Project number:** 5R01AI130156-04
- **Recipient organization:** PENNSYLVANIA STATE UNIV HERSHEY MED CTR
- **Principal Investigator:** Nicholas J Buchkovich
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $375,813
- **Award type:** 5
- **Project period:** 2017-07-17 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9952297

## Citation

> US National Institutes of Health, RePORTER application 9952297, Analysis of the mechanism of HCMV cytoplasmic envelopment (5R01AI130156-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9952297. Licensed CC0.

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