# GENETICS OF HERPESVIRUS - HOST CELL INTERACTIONS

> **NIH NIH R01** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 1993 · $348,031

## Abstract

The analysis of the regulatory phenomena controlling the
coordinately and sequentially ordered synthesis of herpes simplex
virus type I (HSV-1) specific proteins during infection continues
to be the objective of this research.  Two new initiatives are
proposed.  The first is an extension of previous studies on the
regulation of expression of the glycoprotein C (gC) gene, a late
gene.  Late gene expression requires transactivation by the gene
products of two immediate-early genes, ICP4 and ICP27, and has a
strict requirement for the synthesis of viral DNA for expression.
The cis-acting regulatory element controlling gC transcription is
a 15 bp sequence centered around the TATA box.  The requirement
for DNA synthesis can be alleviated by fusing the upstream
transcriptional regulatory sequences of the early tk gene 5' to
the gC TATA element.  The requirement for viral DNA synthesis for
late gene expression will be the main focus of these experiments.
The minimum transcriptional signal capable of giving DNA
replication independent expression of the gC gene will be
determined.  The hypothesis that ICP8, the HSV-1 major DNA
binding protein, functions as a general repressor of late gene
expression prior to DNA replication will be tested.  Using a
virus carrying the tk-gC chimeric gene and a temperature
sensitive mutant allele of the alpha 27 gene, the role of ICP27
in late gene expression will be probed.

Studies have been initiated on the regulation of expression of
the gene for the HSV-1 specified large subunit of ribonucleotide
reductase (RR1).  The RR1 gene shows characteristics of both
immediate-early and early gene regulation and, in contrast to all
other HSV-1 genes, may be uniquely transactivated by ICP0 instead
of ICP4 during infection.  The hypothesis will be tested that in
infection immediate-early expression is achieved through alphaTIF
and the octamer/TAATGARATTC element, while early expression is
accomplished through ICP0 and the downstream regulatory signals
of the RR1 promoter.  The cis-acting signals critical for
transactivation by alpha TIF and ICP0 will be defined.  Exchange
of cis-acting signals between the RR1 promoter and the ICP4
responsive tk promoter should identify the sequences responsive
to induction by ICP0 and ICP4.  Experiments are proposed to
determine if the alpha0 gene product is the only viral
transactivator regulating RR1 expression during the early phase
of infection.  Finally, the RR1 promoter mutant viruses will be
tested in mice for effects on neurovirulence and on the
establishment and reactivation from latency.

## Key facts

- **NIH application ID:** 3127773
- **Project number:** 5R01AI018228-12
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **SAM.gov UEI:** GNJ7BBP73WE9
- **Principal Investigator:** MYRON LEVINE
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1993
- **Award amount:** $348,031
- **Award type:** 5
- **Project period:** 1981-08-01 → 1994-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3127773

## Citation

> US National Institutes of Health, RePORTER application 3127773, GENETICS OF HERPESVIRUS - HOST CELL INTERACTIONS (5R01AI018228-12). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3127773. Licensed CC0.

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