This Article Full Text 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 Silverman, L. R. Articles by Lairmore, M. D. Search for Related Content PubMed PubMed Citation Articles by Silverman, L. R. Articles by Lairmore, M. D.

 Previous Article  |  Next Article 

Journal of Virology, April 2004, p. 3837-3845, Vol. 78, No. 8
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.8.3837-3845.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Human T-Cell Lymphotropic Virus Type 1 Open Reading Frame II-Encoded p30^II Is Required for In Vivo Replication: Evidence of In Vivo Reversion

Center for Retrovirus Research and Department of Veterinary Biosciences,¹ Comprehensive Cancer Center, The Arthur James Cancer Hospital and Research Institute, The Ohio State University, Columbus, Ohio 43210,³ Department of Medicine, Pathology, and Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri 63110²

Received 18 August 2003/ Accepted 22 December 2003

Human T-cell lymphotropic virus type 1 (HTLV-1) causes adult T-cell leukemia/lymphoma and exhibits high genetic stability in vivo. HTLV-1 contains four open reading frames (ORFs) in its pX region. ORF II encodes two proteins, p30^II and p13^II, both of which are incompletely characterized. p30^II localizes to the nucleus or nucleolus and has distant homology to the transcription factors Oct-1, Pit-1, and POU-M1. In vitro studies have demonstrated that at low concentrations, p30^II differentially regulates cellular and viral promoters through an interaction with CREB binding protein/p300. To determine the in vivo significance of p30^II, we inoculated rabbits with cell lines expressing either a wild-type clone of HTLV-1 (ACH.1) or a clone containing a mutation in ORF II, which eliminated wild-type p30^II expression (ACH.30.1). ACH.1-inoculated rabbits maintained higher HTLV-1-specific antibody titers than ACH.30.1-inoculated rabbits, and all ACH.1-inoculated rabbits were seropositive for HTLV-1, whereas only two of six ACH.30.1-inoculated rabbits were seropositive. Provirus could be consistently PCR amplified from peripheral blood mononuclear cell (PBMC) DNA in all ACH.1-inoculated rabbits but in only three of six ACH.30.1-inoculated rabbits. Quantitative competitive PCR indicated higher PBMC proviral loads in ACH.1-inoculated rabbits. Interestingly, sequencing of ORF II from PBMC of provirus-positive ACH.30.1-inoculated rabbits revealed a reversion to wild-type sequence with evidence of early coexistence of mutant and wild-type sequence. Our data provide evidence that HTLV-1 must maintain its key accessory genes to survive in vivo and that in vivo pressures select for maintenance of wild-type ORF II gene products during the early course of infection.

This article has been cited by other articles:

• Taylor, G P (2007). Molecular aspects of HTLV-I infection and adult T-cell leukaemia/lymphoma. J. Clin. Pathol. 60: 1392-1396 [Abstract] [Full Text]  
• Chevalier, S. A., Walic, M., Calattini, S., Mallet, A., Prevost, M.-C., Gessain, A., Mahieux, R. (2007). Construction and Characterization of a Full-Length Infectious Simian T-Cell Lymphotropic Virus Type 3 Molecular Clone. J. Virol. 81: 6276-6285 [Abstract] [Full Text]  
• Miyazaki, M., Yasunaga, J.-I., Taniguchi, Y., Tamiya, S., Nakahata, T., Matsuoka, M. (2007). Preferential Selection of Human T-Cell Leukemia Virus Type 1 Provirus Lacking the 5' Long Terminal Repeat during Oncogenesis. J. Virol. 81: 5714-5723 [Abstract] [Full Text]  
• Asquith, B., Zhang, Y., Mosley, A. J., de Lara, C. M., Wallace, D. L., Worth, A., Kaftantzi, L., Meekings, K., Griffin, G. E., Tanaka, Y., Tough, D. F., Beverley, P. C., Taylor, G. P., Macallan, D. C., Bangham, C. R. M. (2007). In vivo T lymphocyte dynamics in humans and the impact of human T-lymphotropic virus 1 infection. Proc. Natl. Acad. Sci. USA 104: 8035-8040 [Abstract] [Full Text]  
• Miyazato, P., Yasunaga, J.-i., Taniguchi, Y., Koyanagi, Y., Mitsuya, H., Matsuoka, M. (2006). De Novo Human T-Cell Leukemia Virus Type 1 Infection of Human Lymphocytes in NOD-SCID, Common {gamma}-Chain Knockout Mice. J. Virol. 80: 10683-10691 [Abstract] [Full Text]  
• Arnold, J., Yamamoto, B., Li, M., Phipps, A. J., Younis, I., Lairmore, M. D., Green, P. L. (2006). Enhancement of infectivity and persistence in vivo by HBZ, a natural antisense coded protein of HTLV-1. Blood 107: 3976-3982 [Abstract] [Full Text]  
• Hiraragi, H., Kim, S.-J., Phipps, A. J., Silic-Benussi, M., Ciminale, V., Ratner, L., Green, P. L., Lairmore, M. D. (2006). Human T-Lymphotropic Virus Type 1 Mitochondrion-Localizing Protein p13II Is Required for Viral Infectivity In Vivo.. J. Virol. 80: 3469-3476 [Abstract] [Full Text]  
• Younis, I., Boris-Lawrie, K., Green, P. L. (2006). Human T-Cell Leukemia Virus Open Reading Frame II Encodes a Posttranscriptional Repressor That Is Recruited at the Level of Transcription. J. Virol. 80: 181-191 [Abstract] [Full Text]  
• Silverman, L. R., Phipps, A. J., Montgomery, A., Fernandez, S., Tsukahara, T., Ratner, L., Lairmore, M. D. (2005). In vivo analysis of replication and immunogenicity of proviral clones of human T-lymphotropic virus type 1 with selective envelope surface-unit mutations. Blood 106: 3602-3608 [Abstract] [Full Text]  
• Hiraragi, H., Michael, B., Nair, A., Silic-Benussi, M., Ciminale, V., Lairmore, M. (2005). Human T-Lymphotropic Virus Type 1 Mitochondrion-Localizing Protein p13II Sensitizes Jurkat T Cells to Ras-Mediated Apoptosis. J. Virol. 79: 9449-9457 [Abstract] [Full Text]  
• Awasthi, S., Sharma, A., Wong, K., Zhang, J., Matlock, E. F., Rogers, L., Motloch, P., Takemoto, S., Taguchi, H., Cole, M. D., Luscher, B., Dittrich, O., Tagami, H., Nakatani, Y., McGee, M., Girard, A.-M., Gaughan, L., Robson, C. N., Monnat, R. J. Jr., Harrod, R. (2005). A Human T-Cell Lymphotropic Virus Type 1 Enhancer of Myc Transforming Potential Stabilizes Myc-TIP60 Transcriptional Interactions. Mol. Cell. Biol. 25: 6178-6198 [Abstract] [Full Text]  
• Younis, I., Khair, L., Dundr, M., Lairmore, M. D., Franchini, G., Green, P. L. (2004). Repression of Human T-Cell Leukemia Virus Type 1 and Type 2 Replication by a Viral mRNA-Encoded Posttranscriptional Regulator. J. Virol. 78: 11077-11083 [Abstract] [Full Text]