This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Lee, M A Articles by Yates, J L Search for Related Content PubMed PubMed Citation Articles by Lee, M A Articles by Yates, J L

BHRF1 of Epstein-Barr virus, which is homologous to human proto-oncogene bcl2, is not essential for transformation of B cells or for virus replication in vitro.

Department of Human Genetics, Roswell Park Cancer Institute, Buffalo, New York 14263.

ABSTRACT

The Epstein-Barr virus (EBV) genome contains an open reading frame, BHRF1, that encodes a presumptive membrane protein with sequence similarity to the proto-oncogene bcl2, which is linked to human B-cell follicular lymphoma. Potential roles for BHRF1 in EBV's ability to growth transform human B cells and to replicate in B cells in culture were investigated by generating EBV mutants that lack most of the open reading frame. This was accomplished by recombination of plasmids carrying mutations in BHRF1 with the transformation-defective EBV strain P3HR1. Because BHRF1 resides close to the deletion in P3HR1 that renders this strain transformation defective, B-cell transformation could be used to select for recombination events in the region. B-cell clones were established by recombinants which lacked most of the BHRF1 open reading frame, although most of these initial B-cell transformants also carried nonrecombinant (BHRF1+) P3HR1 genomes, at levels ranging from a fraction of a copy to four copies per cell. Secondary B-cell transformants that lacked BHRF1+ EBV at detectable levels were found to release transforming, BHRF1-deficient EBV at levels that were within the normal range for EBV-immortalized B-cell clones. These studies demonstrate that BHRF1 is nonessential for growth transformation of B cells and for virus replication and release from these cells in culture.

This article has been cited by other articles:

• Landais, E., Saulquin, X., Bonneville, M., Houssaint, E. (2005). Long-Term MHC Class II Presentation of the EBV Lytic Protein BHRF1 by EBV Latently Infected B Cells following Capture of BHRF1 Antigen. J. Immunol. 175: 7939-7946 [Abstract] [Full Text]  
• Landais, E., Saulquin, X., Scotet, E., Trautmann, L., Peyrat, M.-A., Yates, J. L., Kwok, W. W., Bonneville, M., Houssaint, E. (2004). Direct killing of Epstein-Barr virus (EBV)-infected B cells by CD4 T cells directed against the EBV lytic protein BHRF1. Blood 103: 1408-1416 [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]  
• 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]  
• Han, I., Harada, S., Weaver, D., Xue, Y., Lane, W., Orstavik, S., Skalhegg, B., Kieff, E. (2001). EBNA-LP Associates with Cellular Proteins Including DNA-PK and HA95. J. Virol. 75: 2475-2481 [Abstract] [Full Text]  
• Delecluse, H-J, Hammerschmidt, W (2000). The genetic approach to the Epstein-Barr virus: from basic virology to gene therapy. Mol. Pathol. 53: 270-279 [Abstract] [Full Text]  
• Norio, P., Schildkraut, C. L., Yates, J. L. (2000). Initiation of DNA Replication within oriP Is Dispensable for Stable Replication of the Latent Epstein-Barr Virus Chromosome after Infection of Established Cell Lines. J. Virol. 74: 8563-8574 [Abstract] [Full Text]  
• Meseda, C. A., Arrand, J. R., Mackett, M. (2000). Herpesvirus papio encodes a functional homologue of the Epstein-Barr virus apoptosis suppressor, BHRF1. J. Gen. Virol. 81: 1801-1805 [Abstract] [Full Text]  
• Bellows, D. S., Chau, B. N., Lee, P., Lazebnik, Y., Burns, W. H., Hardwick, J. M. (2000). Antiapoptotic Herpesvirus Bcl-2 Homologs Escape Caspase-Mediated Conversion to Proapoptotic Proteins. J. Virol. 74: 5024-5031 [Abstract] [Full Text]  
• Paulson, E. J., Speck, S. H. (1999). Differential Methylation of Epstein-Barr Virus Latency Promoters Facilitates Viral Persistence in Healthy Seropositive Individuals. J. Virol. 73: 9959-9968 [Abstract] [Full Text]  
• Marshall, W. L., Yim, C., Gustafson, E., Graf, T., Sage, D. R., Hanify, K., Williams, L., Fingeroth, J., Finberg, R. W. (1999). Epstein-Barr Virus Encodes a Novel Homolog of the bcl-2 Oncogene That Inhibits Apoptosis and Associates with Bax and Bak. J. Virol. 73: 5181-5185 [Abstract] [Full Text]  
• Fingeroth, J. D., Diamond, M. E., Sage, D. R., Hayman, J., Yates, J. L. (1999). CD21-Dependent Infection of an Epithelial Cell Line, 293, by Epstein-Barr Virus. J. Virol. 73: 2115-2125 [Abstract] [Full Text]  
• Virgin, H. W. IV, Presti, R. M., Li, X.-Y., Liu, C., Speck, S. H. (1999). Three Distinct Regions of the Murine Gammaherpesvirus 68 Genome Are Transcriptionally Active in Latently Infected Mice. J. Virol. 73: 2321-2332 [Abstract] [Full Text]  
• Dawson, C. W., Dawson, J., Jones, R., Ward, K., Young, L. S. (1998). Functional Differences between BHRF1, the Epstein-Barr Virus-Encoded Bcl-2 Homologue, and Bcl-2 in Human Epithelial Cells. J. Virol. 72: 9016-9024 [Abstract] [Full Text]  
• Fanidi, A., Hancock, D. C., Littlewood, T. D. (1998). Suppression of c-Myc-Induced Apoptosis by the Epstein-Barr Virus Gene Product BHRF1. J. Virol. 72: 8392-8395 [Abstract] [Full Text]  
• Cheng, E. H.-Y., Nicholas, J., Bellows, D. S., Hayward, G. S., Guo, H.-G., Reitz, M. S., Hardwick, J. M. (1997). A Bcl-2 homolog encoded by Kaposi sarcoma-associated virus, human herpesvirus 8, inhibits apoptosis but does not heterodimerize with Bax or Bak. Proc. Natl. Acad. Sci. USA 94: 690-694 [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]