# STABILITY AND DISEASE TROPISM OF PROVIRAL DNAS

> **NIH NIH R01** · BROWN UNIVERSITY · 1987 · $136,234

## Abstract

We are studying two separate aspects of the biology of avian retroviruses:
the mechanism of induction of avian osteopetrosis and the stability of
proviral DNA.  Avian retroviruses lacking oncogenes often produce primarily
one form of non-acute disease.  We have termed this disease preference
"targeting."  We are interested in defining which sequences in the viral
genome are responsible for osteopetrosis "targeting" as a start to
understanding the mechanism of disease induction.  Our approach has been to
construct a molecular clone of a virus which "targets" toward osteopetrosis
(NTRE-2) and then to construct recombinant viruses by exchanging homologous
restriction endonulease frangments between NTRE-2 and a virus which
"targets" toward the production of lymphoma (RAV-60NY203) or which does not
produce disease (RAV-O).  Results of these studies suggest that sequences
within the LTR are necessary for disease induction but that sequences
within the viral structural genes most probably in gag or pol are required
for the production of osteopetrosis.  This represents the first association
of a viral structural protein with the production of disease.  We will
extend these observations to smaller restriction fragments and ultimately
to the level of DNA sequence analysis and site specific mutagenesis to
define the sequences responsible for osteopetrosis induction.

The similarity in structure between retrovirus proviral DNA and
transposable genetic elements has been frequently commented upon.  There is
however little if any eveidence that proviruses possess any of the
functional characteristics of transposable genetic elements.  We have
observed "instability" in the pattern of proviral DNA in several clones of
td-RSV infected QT-6 cells.  The patterns of "instability" observed include
both loss and gain  of proviral sequences and propagation of deletions into
adjacent cellular DNA.  We intend to use the techniques ol molecular
cloning, DNA sequencing and chromatin structure analysis to determine
whether specific sequences or DNA conformations can be correlated proviral
instability.

## Key facts

- **NIH application ID:** 3170884
- **Project number:** 5R01CA032980-06
- **Recipient organization:** BROWN UNIVERSITY
- **SAM.gov UEI:** E3FDXZ6TBHW3
- **Principal Investigator:** Peter R. Shank
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1987
- **Award amount:** $136,234
- **Award type:** 5
- **Project period:** 1982-07-01 → 1988-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3170884

## Citation

> US National Institutes of Health, RePORTER application 3170884, STABILITY AND DISEASE TROPISM OF PROVIRAL DNAS (5R01CA032980-06). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3170884. Licensed CC0.

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