# VIral and host mechanisms that tilt the HSV lytic/latent balance

> **NIH NIH P01** · HARVARD MEDICAL SCHOOL · 2020 · $2,130,974

## Abstract

Summary/Abstract for Overall Program
The long-term objective of this program project is to determine how herpes simplex virus
1 (HSV-1) can switch between a highly active "lytic" infection that produces infectious
virus and a more silent latent infection. There are several hypotheses regarding
mechanisms that can tilt the balance in favor of lytic infection or latent infection. These
mechanisms include viral gene products that affect the chromatin status of the viral
genome, post-transcriptional mechanisms that can affect viral and host gene expression,
and immune responses and viral gene products that combat those responses. None of
these mechanisms is solely responsible for the lytic/latent balance, and each of these
mechanisms is highly likely to be connected. For example, immune responses can affect
viral gene expression, and post-transcriptional mechanisms can repress the expression
of viral gene products that affect chromatin status and combat immune responses. Thus,
an integrated approach to the lytic/latent balance is needed. In this Program Project
proposal, three senior herpesvirologists with complementary areas of expertise will
conduct a series of highly collaborative studies to investigate these mechanisms in three
intertwined projects with the aid of three cores.
Project 1 will study (including collaborative studies with Project 2) how viral latency-
associated transcripts (LATs), the viral protein ICP0, and the host protein CTCF effect a
chromatin configuration poised for reactivation during establishment and maintenance of
latency in vivo, and with Project 3, in cultured mouse neurons, and in human neurons.
Project 2 will focus on how post-transcriptional regulatory mechanisms can repress lytic
gene expression and affect chromatin status (with Project 1) and a viral gene product
that counteracts immunity (with Projects 3 and 1) and contribute to latency, and a virus
block to nuclear export of miRNAs (with Project 1) and the targets of viral miRNAs in
cultured cells including mouse and human neurons (Projects 3 and 1).
Project 3 will use an in vitro model of latency using cultured neurons from mice, including
genetically altered strains, and viral mutants (some from Projects 1 and 2) to test roles of
neuron-specific autophagosomes, viral proteins that counter immunity, and antibodies in
the nervous system (including those generated by a vaccine from Project 1) in control of
viral replication, latency, reactivation, and, gene expression.

## Key facts

- **NIH application ID:** 9987460
- **Project number:** 5P01AI098681-07
- **Recipient organization:** HARVARD MEDICAL SCHOOL
- **Principal Investigator:** DONALD M COEN
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $2,130,974
- **Award type:** 5
- **Project period:** 2013-07-02 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9987460

## Citation

> US National Institutes of Health, RePORTER application 9987460, VIral and host mechanisms that tilt the HSV lytic/latent balance (5P01AI098681-07). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9987460. Licensed CC0.

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