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Blood, 1 November 2008, Vol. 112, No. 9, pp. 3788-3797. Prepublished online as a Blood First Edition Paper on August 8, 2008; DOI 10.1182/blood-2008-04-154286. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2008-04-154286v1 112/9/3788    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 Arnold, J. Articles by Green, P. L. Search for Related Content PubMed PubMed Citation Articles by Arnold, J. Articles by Green, P. L. Related Collections Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Human T-cell leukemia virus type-1 antisense-encoded gene, Hbz, promotes T-lymphocyte proliferation Joshua Arnold1,2, Bevin Zimmerman1,2, Min Li1,2, Michael D. Lairmore1,2,3,4, and Patrick L. Green1,2,3,4 1 Center for Retrovirus Research, Departments of2 Veterinary Biosciences and Molecular Virology Immunology and 3 Medical Genetics, and 4 Comprehensive Cancer Center and Solove Research Institute, The Ohio State University, Columbus Human T-cell leukemia virus type 1 (HTLV-1) basic leucine zipper factor (HBZ) is dispensable for HTLV-1–mediated cellular transformation in cell culture, but is required for efficient viral infectivity and persistence in rabbits. In most adult T-cell leukemia (ATL) cells, Tax oncoprotein expression is typically low or undetectable, whereas Hbz gene expression is maintained, suggesting that Hbz expression may support infected cell survival and, ultimately, leukemogenesis. Emerging data indicate that HBZ protein can interact with cAMP response element binding protein (CREB) and Jun family members, altering transcription factor binding and transactivation of both viral and cellular promoters. Herein, lentiviral vectors that express Hbz-specific short hairpin (sh)–RNA effectively decreased both Hbz mRNA and HBZ protein expression in transduced HTLV-1–transformed SLB-1 T cells. Hbz knockdown correlated with a significant decrease in T-cell proliferation in culture. Both SLB-1 and SLB-1-Hbz knockdown cells engrafted into inoculated NOD/SCIDchain–/– mice to form solid tumors that also infiltrated multiple tissues. However, tumor formation and organ infiltration were significantly decreased in animals challenged with SLB-1-Hbz knockdown cells. Our data indicate that Hbz expression enhances the proliferative capacity of HTLV-1–infected T cells, playing a critical role in cell survival and ultimately HTLV-1 tumorigenesis in the infected host. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M. Halin, E. Douceron, I. Clerc, C. Journo, N. L. Ko, S. Landry, E. L. Murphy, A. Gessain, I. Lemasson, J.-M. Mesnard, et al. Human T-cell leukemia virus type 2 produces a spliced antisense transcript encoding a protein that lacks a classic bZIP domain but still inhibits Tax2-mediated transcription Blood, September 17, 2009; 114(12): 2427 - 2438. [Abstract] [Full Text] [PDF] 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]

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