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Blood, 1 March 2006, Vol. 107, No. 5, pp. 1980-1988. Prepublished online as a Blood First Edition Paper on November 1, 2005; DOI 10.1182/blood-2005-03-1333. This Article Full Text (PDF) All Versions of this Article: 2005-03-1333v1 107/5/1980    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 Xie, L. Articles by Green, P. L Search for Related Content PubMed PubMed Citation Articles by Xie, L. Articles by Green, P. L Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted April 1, 2005 Accepted October 13, 2005 The PDZ binding motif of HTLV-1 tax promotes virus mediated T-cell proliferation in vitro and persistence in vivo Li Xie, Brenda Yamamoto, Abdelali Haoudi, O J Semmes, and Patrick L Green* Department of Veterinary Biosciences, The Ohio State University, Columbus, Ohio, USA; Center for Retrovirus Research, The Ohio State University, Columbus, Ohio, USA; Comprehensive Cancer Center James Cancer Hospital and Solove Research Institute, The Ohio State University, Columbus, Ohio, USA Department of Microbiology and Molecular Cell Biology, Eastern Virginia Medical School, Norfolk, Virginia, USA Department of Veterinary Biosciences, The Ohio State University, Columbus, Ohio, USA; Department of Molecular Virology, Immunology, and Medical Genetics, The Ohio State University, Columbus, Ohio, USA; Center for Retrovirus Research, The Ohio State University, Columbus, Ohio, USA * Corresponding author; email: green.466{at}osu.edu. HTLV-1 cellular transformation and disease induction is dependent on expression of the viral Tax oncoprotein. PDZ is a modular protein interaction domain used in organizing signaling complexes in eukaryotic cells through recognition of a specific binding motif in partner proteins. Tax-1, but not Tax-2, contains a PDZ-binding domain motif (PBM) that promotes the interaction with several cellular PDZ proteins. Herein, we investigate the contribution of the Tax-1 PBM in HTLV-induced proliferation and immortalization of primary T-cells in vitro and viral survival in an infectious rabbit animal model. We generated several HTLV-1 and HTLV-2 Tax viral mutants including HTLV-1PBM, HTLV-2+C22(+PBM), and HTLV-2+C18(PBM). All Tax mutants maintained the ability to significantly activate the CREB/ATF or NFB signaling pathways. Microtiter proliferation assays revealed that the Tax-1 PBM significantly increases both HTLV-1 and HTLV-2-induced primary T-cell proliferation. In addition, Tax-1 PBM was responsible for the micronuclei induction activity of Tax-1 relative to that of Tax-2. Viral infection and persistence were severely attenuated in rabbits inoculated with HTLV-1PBM. Our results provide the first direct evidence suggesting that PBM-mediated associations between Tax-1 and cellular proteins play a key role in HTLV-induced cell proliferation and genetic instability in vitro and facilitate viral persistence in vivo. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: HTLV tax tails David Derse Blood 2006 107: 1740-1741. [Full Text] [PDF] This article has been cited by other articles: L. Xie, M. Kesic, B. Yamamoto, M. Li, I. Younis, M. D. Lairmore, and P. L. Green Human T-Cell Leukemia Virus Type 2 Rex Carboxy Terminus Is an Inhibitory/Stability Domain That Regulates Rex Functional Activity and Viral Replication J. Virol., May 15, 2009; 83(10): 5232 - 5243. [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] J.-M. Peloponese Jr., J. Yasunaga, T. Kinjo, K. Watashi, and K.-T. Jeang Peptidylproline cis-trans-Isomerase Pin1 Interacts with Human T-Cell Leukemia Virus Type 1 Tax and Modulates Its Activation of NF-{kappa}B J. Virol., April 1, 2009; 83(7): 3238 - 3248. [Abstract] [Full Text] [PDF] V. T. Mihaylova, A. M. Green, M. Khurgel, O. J. Semmes, and G. M. Kupfer Human T-Cell Leukemia Virus I Tax Protein Sensitizes p53-Mutant Cells to DNA Damage Cancer Res., June 15, 2008; 68(12): 4843 - 4852. [Abstract] [Full Text] [PDF] K. Pichler, T. Kattan, J. Gentzsch, A. K. Kress, G. P. Taylor, C. R. M. Bangham, and R. Grassmann Strong induction of 4-1BB, a growth and survival promoting costimulatory receptor, in HTLV-1-infected cultured and patients' T cells by the viral Tax oncoprotein Blood, May 1, 2008; 111(9): 4741 - 4751. [Abstract] [Full Text] [PDF] C. Arpin-Andre and J.-M. Mesnard The PDZ Domain-binding Motif of the Human T Cell Leukemia Virus Type 1 Tax Protein Induces Mislocalization of the Tumor Suppressor hScrib in T cells J. Biol. Chem., November 9, 2007; 282(45): 33132 - 33141. [Abstract] [Full Text] [PDF] M. Higuchi, C. Tsubata, R. Kondo, S. Yoshida, M. Takahashi, M. Oie, Y. Tanaka, R. Mahieux, M. Matsuoka, and M. Fujii Cooperation of NF-{kappa}B2/p100 Activation and the PDZ Domain Binding Motif Signal in Human T-Cell Leukemia Virus Type 1 (HTLV-1) Tax1 but Not HTLV-2 Tax2 Is Crucial for Interleukin-2-Independent Growth Transformation of a T-Cell Line J. Virol., November 1, 2007; 81(21): 11900 - 11907. [Abstract] [Full Text] [PDF] H. Cui, A. Hayashi, H.-S. Sun, M. P. Belmares, C. Cobey, T. Phan, J. Schweizer, M. W. Salter, Y. T. Wang, R. A. Tasker, et al. PDZ Protein Interactions Underlying NMDA Receptor-Mediated Excitotoxicity and Neuroprotection by PSD-95 Inhibitors J. Neurosci., September 12, 2007; 27(37): 9901 - 9915. [Abstract] [Full Text] [PDF] S. A. Chevalier, M. Walic, S. Calattini, A. Mallet, M.-C. Prevost, A. Gessain, and R. Mahieux Construction and Characterization of a Full-Length Infectious Simian T-Cell Lymphotropic Virus Type 3 Molecular Clone J. Virol., June 15, 2007; 81(12): 6276 - 6285. [Abstract] [Full Text] [PDF] B. Asquith, Y. Zhang, A. J. Mosley, C. M. de Lara, D. L. Wallace, A. Worth, L. Kaftantzi, K. Meekings, G. E. Griffin, Y. Tanaka, et al. In vivo T lymphocyte dynamics in humans and the impact of human T-lymphotropic virus 1 infection PNAS, May 8, 2007; 104(19): 8035 - 8040. [Abstract] [Full Text] [PDF] J. Bohl, N. Brimer, C. Lyons, and S. B. Vande Pol The Stardust Family Protein MPP7 Forms a Tripartite Complex with LIN7 and DLG1 That Regulates the Stability and Localization of DLG1 to Cell Junctions J. Biol. Chem., March 30, 2007; 282(13): 9392 - 9400. [Abstract] [Full Text] [PDF] W. M. Switzer, S. H. Qari, N. D. Wolfe, D. S. Burke, T. M. Folks, and W. Heneine Ancient origin and molecular features of the novel human T-lymphotropic virus type 3 revealed by complete genome analysis. J. Virol., August 1, 2006; 80(15): 7427 - 7438. [Abstract] [Full Text] [PDF]

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