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 Bellows, D. S.
Right arrow Articles by Hardwick, J. M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Bellows, D. S.
Right arrow Articles by Hardwick, J. M.

 Previous Article  |  Next Article 

Journal of Virology, June 2000, p. 5024-5031, Vol. 74, No. 11
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Antiapoptotic Herpesvirus Bcl-2 Homologs Escape Caspase-Mediated Conversion to Proapoptotic Proteins

David S. Bellows,1 B. Nelson Chau,1 Percy Lee,2 Yuri Lazebnik,3 William H. Burns,4 and J. Marie Hardwick1,2,*

Departments of Pharmacology and Molecular Sciences1 and Molecular Microbiology and Immunology,2 Johns Hopkins University Schools of Medicine and Public Health, Baltimore, Maryland 21205; Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, 117243; and Medical College of Wisconsin, Milwaukee, Wisconsin 532264

Received 14 September 1999/Accepted 2 March 2000

The antiapoptotic Bcl-2 and Bcl-xL proteins of mammals are converted into potent proapoptotic factors when they are cleaved by caspases, a family of apoptosis-inducing proteases (E. H.-Y. Cheng, D. G. Kirsch, R. J. Clem, R. Ravi, M. B. Kastan, A. Bedi, K. Ueno, and J. M. Hardwick, Science 278:1966-1968, 1997; R. J. Clem, E. H.-Y. Cheng, C. L. Karp, D. G. Kirsch, K. Ueno, A. Takahashi, M. B. Kastan, D. E. Griffin, W. C. Earnshaw, M. A. Veliuona, and J. M. Hardwick, Proc. Natl. Acad. Sci. USA 95:554-559, 1998). Gamma herpesviruses also encode homologs of the Bcl-2 family. All tested herpesvirus Bcl-2 homologs possess antiapoptotic activity, including the more distantly related homologs encoded by murine gammaherpesvirus 68 (gamma HV68) and bovine herpesvirus 4 (BHV4), as described here. To determine if viral Bcl-2 proteins can be converted into death factors, similar to their cellular counterparts, five herpesvirus Bcl-2 homologs from five different viruses were tested for their susceptibility to caspases. Only the viral Bcl-2 protein encoded by gamma HV68 was susceptible to caspase digestion. However, unlike the caspase cleavage products of cellular Bcl-2, Bcl-xL, and Bid, which are potent inducers of apoptosis, the cleavage product of gamma HV68 Bcl-2 lacked proapoptotic activity. KSBcl-2, encoded by the Kaposi's sarcoma-associated herpesvirus, was the only viral Bcl-2 homolog that was capable of killing cells when expressed as an N-terminal truncation. However, because KSBcl-2 was not cleavable by caspases, the latent proapoptotic activity of KSBcl-2 apparently cannot be released. The Bcl-2 homologs encoded by herpesvirus saimiri, Epstein-Barr virus, and BHV4 were not cleaved by apoptotic cell extracts and did not possess latent proapoptotic activities. Thus, herpesvirus Bcl-2 homologs escape negative regulation by retaining their antiapoptotic activities and/or failing to be converted into proapoptotic proteins by caspases during programmed cell death.

* Corresponding author. Mailing address: Dept. of Molecular Microbiology and Immunology, Johns Hopkins, E5132 SPH, 615 North Wolfe St., Baltimore, MD 21205. Phone: (410) 955-2716. Fax: (410) 955-0105. E-mail: hardwick{at}jhu.edu.

Journal of Virology, June 2000, p. 5024-5031, Vol. 74, No. 11
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Jacobs, N., Bartlett, N. W., Clark, R. H., Smith, G. L. (2008). Vaccinia virus lacking the Bcl-2-like protein N1 induces a stronger natural killer cell response to infection. J. Gen. Virol. 89: 2877-2881 [Abstract] [Full Text]  
  • Banadyga, L., Gerig, J., Stewart, T., Barry, M. (2007). Fowlpox Virus Encodes a Bcl-2 Homologue That Protects Cells from Apoptotic Death through Interaction with the Proapoptotic Protein Bak. J. Virol. 81: 11032-11045 [Abstract] [Full Text]  
  • Gillet, L., Dewals, B., Farnir, F., de Leval, L., Vanderplasschen, A. (2005). Bovine Herpesvirus 4 Induces Apoptosis of Human Carcinoma Cell Lines In vitro and In vivo. Cancer Res. 65: 9463-9472 [Abstract] [Full Text]  
  • de Lima, B. D., May, J. S., Marques, S., Simas, J. P., Stevenson, P. G. (2005). Murine gammaherpesvirus 68 bcl-2 homologue contributes to latency establishment in vivo. J. Gen. Virol. 86: 31-40 [Abstract] [Full Text]  
  • Lu, M., Suen, J., Frias, C., Pfeiffer, R., Tsai, M.-H., Chuang, E., Zeichner, S. L. (2004). Dissection of the Kaposi's Sarcoma-Associated Herpesvirus Gene Expression Program by Using the Viral DNA Replication Inhibitor Cidofovir. J. Virol. 78: 13637-13652 [Abstract] [Full Text]  
  • Loh, J., Thomas, D. A., Revell, P. A., Ley, T. J., Virgin, H. W. IV (2004). Granzymes and Caspase 3 Play Important Roles in Control of Gammaherpesvirus Latency. J. Virol. 78: 12519-12528 [Abstract] [Full Text]  
  • Li, Y., Mahajan, N. P., Webster-Cyriaque, J., Bhende, P., Hong, G. K., Earp, H. S., Kenney, S. (2004). The C-Mer Gene Is Induced by Epstein-Barr Virus Immediate-Early Protein BRLF1. J. Virol. 78: 11778-11785 [Abstract] [Full Text]  
  • Seo, S. Y., Chen, Y.-b., Ivanovska, I., Ranger, A. M., Hong, S. J., Dawson, V. L., Korsmeyer, S. J., Bellows, D. S., Fannjiang, Y., Hardwick, J. M. (2004). BAD Is a Pro-survival Factor Prior to Activation of Its Pro-apoptotic Function. J. Biol. Chem. 279: 42240-42249 [Abstract] [Full Text]  
  • Dourmishev, L. A., Dourmishev, A. L., Palmeri, D., Schwartz, R. A., Lukac, D. M. (2003). Molecular Genetics of Kaposi's Sarcoma-Associated Herpesvirus (Human Herpesvirus 8) Epidemiology and Pathogenesis. Microbiol. Mol. Biol. Rev. 67: 175-212 [Abstract] [Full Text]  
  • Flano, E., Kim, I.-J., Moore, J., Woodland, D. L., Blackman, M. A. (2003). Differential {gamma}-Herpesvirus Distribution in Distinct Anatomical Locations and Cell Subsets During Persistent Infection in Mice. J. Immunol. 170: 3828-3834 [Abstract] [Full Text]  
  • Everett, H., Barry, M., Sun, X., Lee, S. F., Frantz, C., Berthiaume, L. G., McFadden, G., Bleackley, R. C. (2002). The Myxoma Poxvirus Protein, M11L, Prevents Apoptosis by Direct Interaction with the Mitochondrial Permeability Transition Pore. JEM 196: 1127-1140 [Abstract] [Full Text]  
  • Feng, P., Park, J., Lee, B.-S., Lee, S.-H., Bram, R. J., Jung, J. U. (2002). Kaposi's Sarcoma-Associated Herpesvirus Mitochondrial K7 Protein Targets a Cellular Calcium-Modulating Cyclophilin Ligand To Modulate Intracellular Calcium Concentration and Inhibit Apoptosis. J. Virol. 76: 11491-11504 [Abstract] [Full Text]  
  • Cuconati, A., White, E. (2002). Viral homologs of BCL-2: role of apoptosis in the regulation of virus infection. Genes Dev. 16: 2465-2478 [Full Text]  
  • Lee, J. M., Lee, K.-H., Weidner, M., Osborne, B. A., Hayward, S. D. (2002). Epstein-Barr virus EBNA2 blocks Nur77- mediated apoptosis. Proc. Natl. Acad. Sci. USA 99: 11878-11883 [Abstract] [Full Text]  
  • Clambey, E. T., Virgin, H. W. IV, Speck, S. H. (2002). Characterization of a Spontaneous 9.5-Kilobase-Deletion Mutant of Murine Gammaherpesvirus 68 Reveals Tissue-Specific Genetic Requirements for Latency. J. Virol. 76: 6532-6544 [Abstract] [Full Text]  
  • Huang, Q., Petros, A. M., Virgin, H. W., Fesik, S. W., Olejniczak, E. T. (2002). Solution structure of a Bcl-2 homolog from Kaposi sarcoma virus. Proc. Natl. Acad. Sci. USA 99: 3428-3433 [Abstract] [Full Text]  
  • Poole, L. J., Yu, Y., Kim, P. S., Zheng, Q.-Z., Pevsner, J., Hayward, G. S. (2002). Altered Patterns of Cellular Gene Expression in Dermal Microvascular Endothelial Cells Infected with Kaposi's Sarcoma-Associated Herpesvirus. J. Virol. 76: 3395-3420 [Abstract] [Full Text]  
  • Bellows, D. S., Howell, M., Pearson, C., Hazlewood, S. A., Hardwick, J. M. (2002). Epstein-Barr Virus BALF1 Is a BCL-2-Like Antagonist of the Herpesvirus Antiapoptotic BCL-2 Proteins. J. Virol. 76: 2469-2479 [Abstract] [Full Text]  
  • Widmer, I., Wernli, M., Bachmann, F., Gudat, F., Cathomas, G., Erb, P. (2002). Differential Expression of Viral Bcl-2 Encoded by Kaposi's Sarcoma-Associated Herpesvirus and Human Bcl-2 in Primary Effusion Lymphoma Cells and Kaposi's Sarcoma Lesions. J. Virol. 76: 2551-2556 [Abstract] [Full Text]  
  • Wakeling, M. N., Roy, D. J., Nash, A. A., Stewart, J. P. (2001). Characterization of the murine gammaherpesvirus 68 ORF74 product: a novel oncogenic G protein-coupled receptor. J. Gen. Virol. 82: 1187-1197 [Abstract] [Full Text]  
  • Afonso, C. L., Tulman, E. R., Lu, Z., Zsak, L., Rock, D. L., Kutish, G. F. (2001). The Genome of Turkey Herpesvirus. J. Virol. 75: 971-978 [Abstract] [Full Text]  
  • Li, L.-Y., Shih, H.-M., Liu, M.-Y., Chen, J.-Y. (2001). The Cellular Protein PRA1 Modulates the Anti-apoptotic Activity of Epstein-Barr Virus BHRF1, a Homologue of Bcl-2, through Direct Interaction. J. Biol. Chem. 276: 27354-27362 [Abstract] [Full Text]  
  • Kerr, D. A., Nery, J. P., Traystman, R. J., Chau, B. N., Hardwick, J. M. (2000). Survival motor neuron protein modulates neuron-specific apoptosis. Proc. Natl. Acad. Sci. USA 97: 13312-13317 [Abstract] [Full Text]  
  • Gangappa, S., van Dyk, L. F., Jewett, T. J., Speck, S. H., Virgin, H. W. IV (2002). Identification of the In Vivo Role of a Viral bcl-2. JEM 195: 931-940 [Abstract] [Full Text]  
  • Blackman, M. A., Flano, E. (2002). Persistent {gamma}-herpesvirus Infections: What Can We Learn from an Experimental Mouse Model?. JEM 195: F29-F32 [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»