# ASSEMBLY OF MURINE LEUKEMIA VIRUSES

> **NIH NIH R01** · LSU HEALTH SCIENCES CENTER · 1989 · $133,421

## Abstract

The morphogenesis of murine retroviruses involves an initial interaction
between two 35s viral RNA genomes and about 2000 Pr65gag polyprotein
precursor molecules to form a nucleoprotein complex and the subsequent
association of the Pr65gag/RNA complex at the cell surface with lipids and
additional envelope proteins to form a nascent, immature particle.
Specific proteolytic cleavages of Pr65gag and envelope proteins during
and/or after budding by specific proteases then leads to maturation of the
virion.  We intend to analyze three aspects of this assembly problem:

i) The mechanism by which the about 2000 Pr65gag precursor molecules are
brought to and then inserted into the plasma membrane.  The recent
discovery that the NH2 terminus of Pr65gag is myristylated has led us to
look at when this modification occurs, e.g., on polysomes?  on
cytoskeletons?  on membranes?  Also, what happens to virus production when
cerulenin, an inhibitor of fatty acid synthesis, is used?  Further, since
p15, the NH2 terminal protein on Pr65gag has a stretch of 20 hydrophobic
amino acids at its NH2 terminus, we want to know what, if any, is more
important for insertion of Pr65gag into the membrane, viz., the myristic
acid modification or the presence of about 20 hydrophobic amino acids?
Appropriate mutations and deletions in cloned p15 MuLV DNA (corresponding
to the NH2 terminus) will be constructed and the DNA will then be used to
answer these questions via transfection or microinjection experiments with
appropriate host cells.

ii) The manner in which the Pr65gag molecules are associated with the
cytoskeleton, e.g., is it necessary to be both myristylated and
under-phosphorylated?  Also, how does this association lead to an
alteration of the actin component of the cytoskeleton?

iii) The molecular basis by which the "immature", Pr65gag enriched C-type
particles are converted by proteolytic cleavage to "mature", C-type virus
particles.  This involves a further study of the murine eetrovirus specific
protease activity.  Toward this end there now appears good evidence that
the protease is virus-coded.  It is located on the genome after gag and
before pol.  We are currently attempting to clone the putative protease
gene and isolate the gene product in sufficient quantities, so that the
above reaction and concomitant maturation can be characterized in molecular
detail.

## Key facts

- **NIH application ID:** 3175243
- **Project number:** 5R01CA037380-07
- **Recipient organization:** LSU HEALTH SCIENCES CENTER
- **SAM.gov UEI:** M7KCJ79FAVH5
- **Principal Investigator:** Ronald B Luftig
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1989
- **Award amount:** $133,421
- **Award type:** 5
- **Project period:** 1983-09-01 → 1990-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3175243

## Citation

> US National Institutes of Health, RePORTER application 3175243, ASSEMBLY OF MURINE LEUKEMIA VIRUSES (5R01CA037380-07). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3175243. Licensed CC0.

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