This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Bonzon, C.
Right arrow Articles by Fan, H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Bonzon, C.
Right arrow Articles by Fan, H.

 Previous Article  |  Next Article 

Journal of Virology, March 1999, p. 2434-2441, Vol. 73, No. 3
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

Christine Bonzon and Hung Fan*

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.


* 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.


Journal of Virology, March 1999, p. 2434-2441, Vol. 73, No. 3
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.



This article has been cited by other articles:

  • Yoshimura, F. K., Luo, X., Zhao, X., Gerard, H. C., Hudson, A. P. (2008). Up-regulation of a cellular protein at the translational level by a retrovirus. Proc. Natl. Acad. Sci. USA 105: 5543-5548 [Abstract] [Full Text]  
  • Zhao, X., Yoshimura, F. K. (2008). Expression of Murine Leukemia Virus Envelope Protein Is Sufficient for the Induction of Apoptosis. J. Virol. 82: 2586-2589 [Abstract] [Full Text]  
  • Yoshimura, F. K., Luo, X. (2007). Induction of Endoplasmic Reticulum Stress in Thymic Lymphocytes by the Envelope Precursor Polyprotein of a Murine Leukemia Virus during the Preleukemic Period. J. Virol. 81: 4374-4377 [Abstract] [Full Text]  
  • Nanua, S., Yoshimura, F. K. (2004). Mink Epithelial Cell Killing by Pathogenic Murine Leukemia Viruses Involves Endoplasmic Reticulum Stress. J. Virol. 78: 12071-12074 [Abstract] [Full Text]  
  • Nanua, S., Yoshimura, F. K. (2004). Differential Cell Killing by Lymphomagenic Murine Leukemia Viruses Occurs Independently of p53 Activation and Mitochondrial Damage. J. Virol. 78: 5088-5096 [Abstract] [Full Text]  
  • Wensel, D. L., Li, W., Cunningham, J. M. (2003). A Virus-Virus Interaction Circumvents the Virus Receptor Requirement for Infection by Pathogenic Retroviruses. J. Virol. 77: 3460-3469 [Abstract] [Full Text]  
  • Kitagawa, M., Yamaguchi, S., Hasegawa, M., Tanaka, K., Sado, T., Hirokawa, K., Aizawa, S. (2002). Friend Leukemia Virus Infection Enhances DNA Damage-Induced Apoptosis of Hematopoietic Cells, Causing Lethal Anemia in C3H Hosts. J. Virol. 76: 7790-7798 [Abstract] [Full Text]  
  • Bolton, D. L., Hahn, B.-I., Park, E. A., Lehnhoff, L. L., Hornung, F., Lenardo, M. J. (2002). Death of CD4+ T-Cell Lines Caused by Human Immunodeficiency Virus Type 1 Does Not Depend on Caspases or Apoptosis. J. Virol. 76: 5094-5107 [Abstract] [Full Text]  
  • Rulli, K., Lenz, J., Levy, L. S. (2002). Disruption of Hematopoiesis and Thymopoiesis in the Early Premalignant Stages of Infection with SL3-3 Murine Leukemia Virus. J. Virol. 76: 2363-2374 [Abstract] [Full Text]  
  • Yoshimura, F. K., Wang, T., Nanua, S. (2001). Mink Cell Focus-Forming Murine Leukemia Virus Killing of Mink Cells Involves Apoptosis and Superinfection. J. Virol. 75: 6007-6015 [Abstract] [Full Text]  
  • Yoshimura, F. K., Wang, T., Yu, F., Kim, H.-R. C., Turner, J. R. (2000). Mink Cell Focus-Forming Murine Leukemia Virus Infection Induces Apoptosis of Thymic Lymphocytes. J. Virol. 74: 8119-8126 [Abstract] [Full Text]  
  • Bonzon, C., Fan, H. (2000). Moloney Murine Leukemia Virus-Induced Tumors Show Altered Levels of Proapoptotic and Antiapoptotic Proteins. J. Virol. 74: 8151-8158 [Abstract] [Full Text]  
  • Adkins, B., Charyulu, V., Sun, Q.-L., Lobo, D., Lopez, D. M. (2000). Early Block in Maturation Is Associated with Thymic Involution in Mammary Tumor-Bearing Mice. J. Immunol. 164: 5635-5640 [Abstract] [Full Text]  
  • Lander, J. K., Chesebro, B., Fan, H. (1999). Appearance of Mink Cell Focus-Inducing Recombinants during In Vivo Infection by Moloney Murine Leukemia Virus (M-MuLV) or the Mo+PyF101 M-MuLV Enhancer Variant: Implications for Sites of Generation and Roles in Leukemogenesis. J. Virol. 73: 5671-5680 [Abstract] [Full Text]