# Herpes simplex virus-mediated regulation of host gene expression

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA-IRVINE · 2020 · $350,663

## Abstract

Project summary:
Herpes simplex virus 1 (HSV-1) is a highly contagious pathogen that causes a number
of diseases ranging from painful skin lesions to keratitis and encephalitis. The gene
expression program of HSV-1 has been extensively studied for the past several
decades. Despite the intensive effort, however, it remains unclear how HSV-1
suppresses host gene expression to allow efficient viral replication. Genetic studies have
demonstrated that ICP27, encoded by an essential immediate early gene, plays an
essential role in the inhibition of host mRNA biogenesis. Based on in vitro assays, earlier
studies have suggested that ICP27 blocks transcription and splicing of host genes.
Through high throughput analyses of host gene expression following HSV-1 infection or
ICP27 overexpression, however, recent studies detected no global inhibition of either
transcription or splicing, but only splicing changes in a small number of genes.
Interestingly, these studies found that there was widespread transcription termination
defect in HSV-1-infected cells and that this inhibition was specific to host genes.
Although these recent studies provided important insight into HSV-1-induced host
shutoff, the molecular mechanisms underlying HSV-1-mediated block of transcription
termination remain completely unknown and it is unclear whether such a block is
required for efficient viral replication. We aim to address these important questions in
this proposal. In our preliminary studies, we found that ICP27 specifically interacts with
the essential mRNA 3' processing factor CPSF and that ICP27 blocks mRNA 3'
processing. Since mRNA 3' processing is required for transcription termination, we will
test the hypothesis that ICP27 inhibits host transcription termination by blocking mRNA
3' processing via CPSF, and that ICP27-mediated disruption of host mRNA processing
is important for HSV replication.

## Key facts

- **NIH application ID:** 9884790
- **Project number:** 5R01GM128441-03
- **Recipient organization:** UNIVERSITY OF CALIFORNIA-IRVINE
- **Principal Investigator:** Rozanne M Sandri-Goldin
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $350,663
- **Award type:** 5
- **Project period:** 2018-05-01 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9884790

## Citation

> US National Institutes of Health, RePORTER application 9884790, Herpes simplex virus-mediated regulation of host gene expression (5R01GM128441-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9884790. Licensed CC0.

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