# HERPES SIMPLEX VIRUS MULTIPLICATION

> **NIH NIH R01** · UNIVERSITY OF CHICAGO · 1988 · $143,456

## Abstract

Newly replicated DNA molecules of herpes simplex viruses 1 and 2 (HSV-1 and
HSV-2) consist of head-to-tail concatemers arising most likely by rolling
circle replication.  The large concatemers are subsequently cleaved to
generate unit length molecules which are packaged into viral nucleocapsids.
Cleavage occurs within the a sequences situated at the junctions between
adjacent viral genomes in the concatemers.  In previous studies under this
project we have employed constructed defective virus genomes to investigate
the mechanisms of concatemeric cleavage.  Constructed defective genome
concatemers were generated by replication of seed monomeric repeats
containing a viral DNA replication origin and an a sequence, containing a
cleavage/packaging signal.  These studies have revealed that concatemeric
cleavage was coupled to the packaging of viral DNA.  Analyses of the
structural features of concatemeric junctions and generated termini in
packaged and free nuclear and cytoplasmic DNAs have yielded evidence
concerning details of the cleavage/packaging process, including the
recognition of two signals located within the a sequence which play
distinct roles in the cleavage/packaging; the amplification of a sequences
which is coupled to cleavage, the scanning of the viral DNA concatemers
during packaging for a directly repeated a sequence containing the terminal
cleavage signal, and the requirement for full length encapsidated DNA
genomes for further maturation of nuclear capsids into enveloped
cytoplasmic virions.  On the basis of the data two models were formulated
to explain the known properties of a sequences in standard as well as
defective virus DNA.  We now propose three sets of studies to continue our
analyses of early events in the packaging process.  In the first set of
studies we will continue our investigations of the mechanism of
concatemeric DNA cleavage, through testing and refining various features of
the models proposed.  In the second set of studies we will continue our
analyses of in vivo intermediates in the packaging process.  The third set
of studies will attempt to develop an in vitro system for the cleavage and
possibly encapsidation of HSV DNA.  It is expected that these studies will
uniquely increase our understanding of events constituting the culmination
of the infectious cycle, and involving highly specific DNA-protein and
protein-protein interactions.

## Key facts

- **NIH application ID:** 3126200
- **Project number:** 5R01AI015488-10
- **Recipient organization:** UNIVERSITY OF CHICAGO
- **SAM.gov UEI:** ZUE9HKT2CLC9
- **Principal Investigator:** NIZA B FRENKEL
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1988
- **Award amount:** $143,456
- **Award type:** 5
- **Project period:** 1978-12-01 → 1991-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3126200

## Citation

> US National Institutes of Health, RePORTER application 3126200, HERPES SIMPLEX VIRUS MULTIPLICATION (5R01AI015488-10). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3126200. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*