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Journal of Virology, March 1999, p. 2434-2441, Vol. 73, No. 3
Department of Molecular Biology and
Biochemistry and Cancer Research Institute, University of
California, Irvine, California 92697
Received 2 July 1998/Accepted 24 November 1998
Moloney murine leukemia virus (M-MuLV) is a replication-competent,
simple retrovirus that induces T-cell lymphoma with a mean latency of 3 to 4 months. During the preleukemic period (4 to 10 weeks
postinoculation) a marked decrease in thymic size is apparent for
M-MuLV-inoculated mice in comparison to age-matched uninoculated mice.
We were interested in studying whether the thymic regression was due to
an increased rate of thymocyte apoptosis in the thymi of
M-MuLV-inoculated mice. Neonatal NIH/Swiss mice were inoculated
subcutaneously (s.c.) with wild-type M-MuLV (approximately 105 XC PFU). Mice were sacrificed at 4 to 11 weeks
postinoculation. Thymic single-cell suspensions were prepared and
tested for apoptosis by two-parameter flow cytometry. Indications of
apoptosis included changes in cell size and staining with
7-aminoactinomycin D or annexin V. The levels of thymocyte apoptosis
were significantly higher in M-MuLV-inoculated mice than in
uninoculated control animals, and the levels of apoptosis were
correlated with thymic atrophy. To test the relevance of enhanced
thymocyte apoptosis to leukemogenesis, mice were inoculated with the
Mo+PyF101 enhancer variant of M-MuLV. When inoculated
intraperitoneally, a route that results in wild-type M-MuLV
leukemogenesis, mice displayed levels of enhanced thymocyte apoptosis
comparable to those seen with wild-type M-MuLV. However, in mice
inoculated s.c., a route that results in attenuated leukemogenesis,
significantly lower levels of apoptosis were observed. This supported a
role for higher levels of thymocyte apoptosis in M-MuLV leukemogenesis.
To examine the possible role of mink cell focus-forming (MCF)
recombinant virus in raising levels of thymocyte apoptosis,
MCF-specific focal immunofluorescence assays were performed on
thymocytes from preleukemic mice inoculated with M-MuLV and Mo+PyF101
M-MuLV. The results indicated that infection of thymocytes by MCF virus
recombinants is not required for the increased level of apoptosis and
thymic atrophy.
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
Moloney Murine Leukemia Virus-Induced Preleukemic
Thymic Atrophy and Enhanced Thymocyte Apoptosis Correlate with
Disease Pathogenicity
*
Corresponding author. Mailing address: Department of
Molecular Biology and Biochemistry and Cancer Research Institute,
Biological Sciences II, Rm. 3221, University of California, Irvine, CA
92697. Phone: (949) 824-5554. Fax: (949) 824-4023. E-mail:
hyfan{at}uci.edu.
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