# Function of virion-associated ICP4 in HSV-1 infection

> **NIH NIH R21** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2020 · $234,750

## Abstract

The ICP4 protein of Herpes Simplex Virus type 1 (HSV-1) is essential for virus growth,
and its known functions are to activate the transcription of most HSV genes and repress the
transcription of a few genes known to date. It executes these functions by binding to the
genome and interacting with a number of cellular complexes involved in transcription, including
TFIID, and the mediator complex. These functions are carried out by ICP4 expressed very early
in infection. However, ICP4 is also packaged in the virion tegument. Therefore, the possibility
that ICP4 delivered by the virus itself contributes to the transcription of viral genes in vitro, or in
neurons in vivo, cannot be ruled out. In this scenario, ICP4 would function in a manner similar to
VP16. However, ICP4 is a large and structurally complex protein, and despite our past
comprehensive analyses of ICP4-interacting partners in the nucleus, it remains possible that
ICP4 interacts with viral and cellular proteins in the cytoplasm that have nothing to do with
transcription, and that it functions in other as yet unknown processes in viral infection.
 In this proposal, we present preliminary data showing that is possible to make infectious
virus that does not contain ICP4 in the virion. We also show that ICP4 delivered by the virus
particle associates with viral DNA as it does when ICP4 is expressed by the virus. These two
observations along with the biological and technical tools available to our laboratory will allow us
to determine the involvement of virion-associated ICP4 (vICP4) in infection. In this exploratory
grant, we will test several viable hypotheses regarding the function of vICP4 in gene expression,
innate immunity, and transport to the nucleus. Three aims are proposed to test aspects of our
hypotheses; 1. determine the composition of virions with and without vICP4, 2. determine the
fate and consequences of vICP4, and 3. characterize the parameters of infection of viruses with
and without vICP4 in the mouse ocular model. Completion of the aims of this exploratory study
will enable future more focused studies on the mechanism(s) underlying the function of vICP4,
its role in pathogenesis, and the potential use of mutants lacking virion ICP4 as replication
competent vaccines or vaccine vectors.
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## Key facts

- **NIH application ID:** 9828632
- **Project number:** 5R21AI143179-02
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Neal A. DeLuca
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $234,750
- **Award type:** 5
- **Project period:** 2018-11-23 → 2021-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9828632

## Citation

> US National Institutes of Health, RePORTER application 9828632, Function of virion-associated ICP4 in HSV-1 infection (5R21AI143179-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9828632. Licensed CC0.

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