# MURINE LEUKEMIA VIRUS PATHOGENESIS & IN VIVO EXPRESSION

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA-IRVINE · 1992 · $235,496

## Abstract

We will continue our studies on factors influencing in vivo pathogenesis
and tissue specific infection by Moloney murine leukemia virus (M-MuLV),
which induces T-lymphoma in mice.  These experiments will exploit novel LTR
variants of M-MuLV that show altered disease patterns or tissue
distributions.  There are three major aims: 1) Studies on MCFs and
preleukemic events induced by M-MuLV.  Comparisons between wild-type and
poorly leukemogenic Mo+PyF1O1 M-MuLV identified a preleukemic state of
generalized hematopoietic hyperplasia in the spleen.  This preleukemic
state involves MCF recombinant viruses.  In tile proposed experiments, we
will study events involved in MCF formation in vivo.  We will identify
cells in the mouse involved in both MCF generation and propagation by a
combination of virological and immunological approaches.  The validity of
these results will be tested by studying animals infected with Mo+PyF101
M-MULV, since they do not develop MCFs in vivo.   The molecular basis for
the inability of Mo+PyF101 MCFs to propagate in vivo will be studied. 2)
Leukemogenesis by enhancer variants of M-MuLV.  In contrast to wildtype
M-MuLV, Delta Mo+SV M-MuLV induces B-lymphoma with extremely long latency.
The mechanisms of leukemogenesis will be studied, including virological
parameters, and activation of proto-oncogenes.  The possibility of novel
activated proto-oncogenes will be tested by PCR cloning.  Sublethal
irradiation markedly accelerates leukemogenesis by Delta Mo + SV M-MuLV,
and the mechanism of this will be explored.  A second virus, Delta 27A
M-MuLV induces leukemia of diverse types, including T-lymphoid, B-lymphoid,
myeloid and erythroid.  Leukemogenesis by this virus will be explored as
well. 3) Tissue distribution of Delta Mo+TTR(PD) M-MuLV.  This virus is
driven by regulatory elements of the mouse transthyretin (TTR) gene.  It
shows novel expression sites in vivo: the brain and (in some animals) the
liver.  The particular brain cells infected will be identified, and we will
also seek co-factors for virus expression in the liver.

These experiments will provide insight into the multi-step leukemogenic
process from M-MuLv, they may also elucidate factors involved in
tissue-specific virus infection in vivo.

## Key facts

- **NIH application ID:** 3170372
- **Project number:** 2R01CA032455-12
- **Recipient organization:** UNIVERSITY OF CALIFORNIA-IRVINE
- **SAM.gov UEI:** MJC5FCYQTPE6
- **Principal Investigator:** HUNG Y. FAN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1992
- **Award amount:** $235,496
- **Award type:** 2
- **Project period:** 1982-02-01 → 1996-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3170372

## Citation

> US National Institutes of Health, RePORTER application 3170372, MURINE LEUKEMIA VIRUS PATHOGENESIS & IN VIVO EXPRESSION (2R01CA032455-12). Retrieved via MORVS 2026-10-24 from https://api.morvs.ai/grant/nih/3170372. Licensed CC0.

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