Moloney murine leukemia virus-induced preleukemic thymic atrophy and enhanced thymocyte apoptosis correlate with disease pathogenicity

被引:23
作者
Bonzon, C
Fan, H
机构
[1] Univ Calif Irvine, Dept Mol Biol & Biochem, Irvine, CA 92697 USA
[2] Univ Calif Irvine, Canc Res Inst, Irvine, CA 92697 USA
关键词
D O I
10.1128/JVI.73.3.2434-2441.1999
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
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 10(5) XC PFU). Mice were sacrificed at 4 to 11 weeks postinoculation, Thymic single-cell suspensions were prepared and tested for apoptosis by two-parameter how 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 wildtype 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.
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页码:2434 / 2441
页数:8
相关论文
共 32 条
[1]  
ANDREE HAM, 1990, J BIOL CHEM, V265, P4923
[2]   RECOMBINANT MINK CELL FOCUS-INDUCING VIRUS AND LONG TERMINAL REPEAT ALTERATIONS ACCOMPANY THE INCREASED LEUKEMOGENICITY OF THE MO+PYF101 VARIANT OF MOLONEY MURINE LEUKEMIA-VIRUS AFTER INTRAPERITONEAL INOCULATION [J].
BELLI, B ;
PATEL, A ;
FAN, H .
JOURNAL OF VIROLOGY, 1995, 69 (02) :1037-1043
[3]   THE LEUKEMOGENIC POTENTIAL OF AN ENHANCER VARIANT OF MOLONEY MURINE LEUKEMIA-VIRUS VARIES WITH THE ROUTE OF INOCULATION [J].
BELLI, B ;
FAN, H .
JOURNAL OF VIROLOGY, 1994, 68 (11) :6883-6889
[4]   AN ENHANCER VARIANT OF MOLONEY MURINE LEUKEMIA-VIRUS DEFECTIVE IN LEUKEMOGENESIS DOES NOT GENERATE DETECTABLE MINK CELL FOCUS-INDUCING VIRUS INVIVO [J].
BRIGHTMAN, BK ;
REIN, A ;
TREPP, DJ ;
FAN, H .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1991, 88 (06) :2264-2268
[5]   CHARACTERIZATION OF MONOCLONAL-ANTIBODIES REACTIVE WITH MURINE LEUKEMIA VIRUSES - USE IN ANALYSIS OF STRAINS OF FRIEND MCF AND FRIEND ECOTROPIC MURINE LEUKEMIA-VIRUS [J].
CHESEBRO, B ;
BRITT, W ;
EVANS, L ;
WEHRLY, K ;
NISHIO, J ;
CLOYD, M .
VIROLOGY, 1983, 127 (01) :134-148
[6]  
COHEN JJ, 1991, ADV IMMUNOL, V50, P55
[7]  
COHEN JJ, 1993, IMMUNOL TODAY, V14, P126, DOI 10.1016/0167-5699(93)90214-6
[8]  
CUYPERS HT, 1984, CELL, V37, P141
[9]  
Darzynkiewicz Z, 1997, CYTOMETRY, V27, P1
[10]   SUPPRESSION OF LEUKEMIA-VIRUS PATHOGENICITY BY POLYOMA-VIRUS ENHANCERS [J].
DAVIS, B ;
LINNEY, E ;
FAN, H .
NATURE, 1985, 314 (6011) :550-553