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Prepublished online as a Blood First Edition Paper on August 7, 2003; DOI 10.1182/blood-2003-05-1490. This Article 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 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 Social Bookmarking                   What's this? Submitted May 9, 2003 Accepted July 29, 2003 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* Department of Veterinary Biosciences, The Ohio State University, Columbus, OH, USA; Departments of Molecular Virology, Immunology, and Medical Genetics, The Ohio State University, Columbus, OH, USA; Center for Retrovirus Research and Comprehensive Cancer Center and Solove Research Institute, The Ohio State University, Columbus, OH, USA * Corresponding author; email: green.466{at}osu.edu. HTLV-1 is associated with leukemia/lymphoma and neurological 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 PBMCs resulted in sustained 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: M. Li, M. Kesic, H. Yin, L. Yu, and P. L. Green Kinetic Analysis of Human T-Cell Leukemia Virus Type 1 Gene Expression in Cell Culture and Infected Animals J. Virol., April 15, 2009; 83(8): 3788 - 3797. [Abstract] [Full Text] [PDF] 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. 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