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Blood, 1 December 2003, Vol. 102, No. 12, pp. 3963-3969. Prepublished online as a Blood First Edition Paper on August 7, 2003; DOI 10.1182/blood-2003-05-1490. This Article Full Text Full Text (PDF) All Versions of this Article: 2003-05-1490v1 102/12/3963    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Ye, J. Articles by Green, P. L. Search for Related Content PubMed PubMed Citation Articles by Ye, J. Articles by Green, P. L. Related Collections Oncogenes and Tumor Suppressors Hematopoiesis and Stem Cells Immunobiology Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMATOPOIESIS HTLV-1 Rex is required for viral spread and persistence in vivo but is dispensable for cellular immortalization in vitro Jianxin Ye, Lee Silverman, Michael D. Lairmore, and Patrick L. Green From the Departments of Veterinary Biosciences and Molecular Virology, Immunology, and Medical Genetics; the Center for Retrovirus Research, and the Comprehensive Cancer Center and Solove Research Institute, The Ohio State University, Columbus. Human T-cell leukemia virus type 1 (HTLV-1) is associated with leukemia/lymphoma and neurologic disorders. Although the viral transcriptional activator Tax is the critical viral oncoprotein, Rex, which regulates the expression of the viral structural and enzymatic genes, is essential for efficient viral replication. Herein, we investigate the contribution of Rex in HTLV-1 immortalization of primary T cells in vitro and viral survival in an infectious rabbit animal model. A Rex-deficient HTLV-1 (HTLVRex-) was constructed and characterized for viral gene expression, protein production, and immortalization capacity. Cells transiently transfected with the HTLVRex- proviral clone produced low detectable levels of p19 Gag. 729HTLVRex- stable transfectants produced functional Tax, but undetectable levels of Rex or p19 Gag. Coculture of irradiated 729HTLVRex- cells with peripheral blood mononuclear cells (PBMCs) resulted in sustained interleukin-2 (IL-2)-dependent growth of primary T lymphocytes. These cells carried the HTLVRex- genome and expressed tax/rex mRNA but produced no detectable Rex or p19 Gag. Rabbits inoculated with irradiated 729HTLVRex- cells or 729HTLVRex- cells transiently transfected with a Rex cDNA expression plasmid failed to become persistently infected or mount a detectable antibody response to the viral gene products. Together, our results provide the first direct evidence that Rex and its function to modulate viral gene expression and virion production is not required for in vitro immortalization by HTLV-1. However, Rex is critical for efficient infection of cells and persistence in vivo. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: C. Bolinger, A. Yilmaz, T. R. Hartman, M. B. Kovacic, S. Fernandez, J. Ye, M. Forget, P. L. Green, and K. Boris-Lawrie RNA helicase A interacts with divergent lymphotropic retroviruses and promotes translation of human T-cell leukemia virus type 1 Nucleic Acids Res., April 10, 2007; (2007) gkm124v1. [Abstract] [Full Text] [PDF] I. Lemasson, M. R. Lewis, N. Polakowski, P. Hivin, M.-H. Cavanagh, S. Thebault, B. Barbeau, J. K. Nyborg, and J.-M. Mesnard Human T-Cell Leukemia Virus Type 1 (HTLV-1) bZIP Protein Interacts with the Cellular Transcription Factor CREB To Inhibit HTLV-1 Transcription J. Virol., February 15, 2007; 81(4): 1543 - 1553. [Abstract] [Full Text] [PDF] J. Arnold, B. Yamamoto, M. Li, A. J. Phipps, I. Younis, M. D. Lairmore, and P. L. Green Enhancement of infectivity and persistence in vivo by HBZ, a natural antisense coded protein of HTLV-1 Blood, May 15, 2006; 107(10): 3976 - 3982. [Abstract] [Full Text] [PDF] H. Hiraragi, S.-J. Kim, A. J. Phipps, M. Silic-Benussi, V. Ciminale, L. Ratner, P. L. Green, and M. D. Lairmore Human T-Lymphotropic Virus Type 1 Mitochondrion-Localizing Protein p13II Is Required for Viral Infectivity In Vivo. J. Virol., April 1, 2006; 80(7): 3469 - 3476. [Abstract] [Full Text] [PDF] L. Xie, B. Yamamoto, A. Haoudi, O. J. Semmes, and P. L. Green PDZ binding motif of HTLV-1 Tax promotes virus-mediated T-cell proliferation in vitro and persistence in vivo Blood, March 1, 2006; 107(5): 1980 - 1988. [Abstract] [Full Text] [PDF] I. Younis, B. Yamamoto, A. Phipps, and P. L. Green Human T-Cell Leukemia Virus Type 1 Expressing Nonoverlapping Tax and Rex Genes Replicates and Immortalizes Primary Human T Lymphocytes but Fails To Replicate and Persist In Vivo J. Virol., December 1, 2005; 79(23): 14473 - 14481. [Abstract] [Full Text] [PDF] L. R. Silverman, A. J. Phipps, A. Montgomery, S. Fernandez, T. Tsukahara, L. Ratner, and M. D. Lairmore In vivo analysis of replication and immunogenicity of proviral clones of human T-lymphotropic virus type 1 with selective envelope surface-unit mutations Blood, November 15, 2005; 106(10): 3602 - 3608. [Abstract] [Full Text] [PDF] I. Younis, L. Khair, M. Dundr, M. D. Lairmore, G. Franchini, and P. L. Green Repression of Human T-Cell Leukemia Virus Type 1 and Type 2 Replication by a Viral mRNA-Encoded Posttranscriptional Regulator J. Virol., October 15, 2004; 78(20): 11077 - 11083. [Abstract] [Full Text] [PDF] L. R. Silverman, A. J. Phipps, A. Montgomery, L. Ratner, and M. D. Lairmore Human T-Cell Lymphotropic Virus Type 1 Open Reading Frame II-Encoded p30II Is Required for In Vivo Replication: Evidence of In Vivo Reversion J. Virol., April 15, 2004; 78(8): 3837 - 3845. [Abstract] [Full Text] [PDF]

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