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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 (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 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 Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted April 28, 2008 Accepted July 25, 2008 Human T-cell Leukemia Virus Type-1 Antisense-encoded Gene, Hbz, Promotes T Lymphocyte Proliferation Joshua Arnold, Bevin Zimmerman, Min Li, Michael D Lairmore, and Patrick L Green* Center for Retrovirus Research, The Ohio State University, Columbus, Ohio, United States Department of Veterinary Biosciences, The Ohio State University, Columbus, Ohio, United States Molecular Virology Immunology and Medical Genetics, The Ohio State University, Columbus, Ohio, United States Comprehensive Cancer Center and Solove Research Institute, The Ohio State University, Columbus, Ohio, United States * Corresponding author; email: green.466{at}osu.edu. 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 indicates that HBZ protein can interact with 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 was significantly decreased in animals challenged with SLB-1-Hbz knockdown cells. Taken together 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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