# RETROVIRAL PROTEINS INVOLVED IN DNA INTEGRATION/VIRION

> **NIH NIH R01** · CASE WESTERN RESERVE UNIVERSITY · 1990 · $214,063

## Abstract

The goal of this research is to define biochemical mechanisms of
avian retrovirus replication through the study of the interactions
of viral proteins with nucleic acids.  These multidisciplinary
model studies have direct application to development of anti-HIV
agents.

The first aim of this proposal is to study the interaction of the
viral gag nucleocapsid (NC) and matrix (MA) proteins and their
Pr76gag precursor with viral RNA and to evaluate their role in
virion assembly.  Molecular genetic techniques will be used to make
amino acid substitutions at highly conserved or biochemically
important residues of the NC and MA proteins.  The effect these
changes have on viral replication in vivo and on the biochemical
properties of the mutant proteins purified either from virus or
bacteria will be determined.  The role of the Pr76gag or NC and MA
proteins in the recognition of specific packaging signals in viral
RNA will also be studied.

The second aim of this proposal is to elucidate the mechanism of
action of the DNA endonuclease associated with the viral
integration (IN) protein and its role in viral DNA integration.
Biochemical and molecular genetic experiments are outlined to
relate the sequences at the termini of long terminal repeats (LTR)
of viral DNA required for specific cleavage in vitro by the IN
protein to those required for integration in vivo.  This will be
accomplished by analyzing the effect of small U5 LTR deletions on
both cleavage and on integration of viral DNA.  The requirement for
inverted repeat sequences in the LTR in linear and supercoiled DNA
substrates for IN protein activity and integration in vivo will be
evaluated.  Reconstitution of a viral DNA integration system in
vitro using purified components will be attempted.  In a related
project, the role of secondary structure in the U5 region of viral
RNA for initiation of reverse transcription will be studied.  The
observation that such structures potentially exist in other
retrovirus RNAs including HIV suggest that this is a general
phenomenon of replication.

## Key facts

- **NIH application ID:** 3176063
- **Project number:** 5R01CA038046-07
- **Recipient organization:** CASE WESTERN RESERVE UNIVERSITY
- **SAM.gov UEI:** HJMKEF7EJW69
- **Principal Investigator:** JONATHAN P LEIS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1990
- **Award amount:** $214,063
- **Award type:** 5
- **Project period:** 1984-07-01 → 1994-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3176063

## Citation

> US National Institutes of Health, RePORTER application 3176063, RETROVIRAL PROTEINS INVOLVED IN DNA INTEGRATION/VIRION (5R01CA038046-07). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3176063. Licensed CC0.

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