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Blood, 15 September 2005, Vol. 106, No. 6, pp. 2059-2068. Prepublished online as a Blood First Edition Paper on May 31, 2005; DOI 10.1182/blood-2005-03-0932. This Article Full Text Full Text (PDF) All Versions of this Article: 2005-03-0932v1 106/6/2059    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 Muthumani, K. Articles by Weiner, D. B. Search for Related Content PubMed PubMed Citation Articles by Muthumani, K. Articles by Weiner, D. B. Related Collections Signal Transduction Immunobiology Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY HIV-1 Nef-induced FasL induction and bystander killing requires p38 MAPK activation Karuppiah Muthumani, Andrew Y. Choo, Daniel S. Hwang, Arumugam Premkumar, Nathanael S. Dayes, Crafford Harris, Douglas R. Green, Scott A. Wadsworth, John J. Siekierka, and David B. Weiner From the Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA; the Memorial Sloan-Kettering Cancer Center, New York, NY; Johnson & Johnson Pharmaceutical Research and Development, Raritan, NJ; La Jolla Institute for Allergy and Immunology, San Diego, CA; and the Department of Cell Biology, Harvard Medical School, Boston, MA. The human immunodeficiency virus (HIV) has been reported to target noninfected CD4 and CD8 cells for destruction. This effect is manifested in part through up-regulation of the death receptor Fas ligand (FasL) by HIV-1 negative factor (Nef), leading to bystander damage. However, the signal transduction and transcriptional regulation of this process remains elusive. Here, we provide evidence that p38 mitogen-activated protein kinase (MAPK) is required for this process. Loss-of-function experiments through dominant-negative p38 isoform, p38 siRNA, and chemical inhibitors of p38 activation suggest that p38 is necessary for Nef-induced activator protein-1 (AP-1) activation, as inhibition leads to an attenuation of AP-1-dependent transcription. Furthermore, mutagenesis of the FasL promoter reveals that its AP-1 enhancer element is required for Nef-mediated transcriptional activation. Therefore, a linear pathway for Nef-induced FasL expression that encompasses p38 and AP-1 has been elucidated. Furthermore, chemical inhibition of the p38 pathway attenuates HIV-1-mediated bystander killing of CD8 cells in vitro. (Blood. 2005;106:2059-2068) CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: p38 MAP kinase in HIV-1 infection: the enemy within Jean-Luc Perfettini and Guido Kroemer Blood 2005 106: 1899-1900. [Full Text] [PDF] This article has been cited by other articles: D. Gutierrez-Sanmartin, E. Varela-Ledo, A. Aguilera, S. Romero-Yuste, P. Romero-Jung, A. Gomez-Tato, and B. J. Regueiro Implication of p38 mitogen-activated protein kinase isoforms ({alpha}, {beta}, {gamma} and {delta}) in CD4+ T-cell infection with human immunodeficiency virus type I J. Gen. Virol., July 1, 2008; 89(7): 1661 - 1671. [Abstract] [Full Text] [PDF] B. Majumder, N. J. Venkatachari, E. A. Schafer, M. L. Janket, and V. Ayyavoo Dendritic Cells Infected with vpr-Positive Human Immunodeficiency Virus Type 1 Induce CD8+ T-Cell Apoptosis via Upregulation of Tumor Necrosis Factor Alpha J. Virol., July 15, 2007; 81(14): 7388 - 7399. [Abstract] [Full Text] [PDF] S. A. Trushin, A. Algeciras-Schimnich, S. R. Vlahakis, G. D. Bren, S. Warren, D. J. Schnepple, and A. D. Badley Glycoprotein 120 Binding to CXCR4 Causes p38-Dependent Primary T Cell Death That Is Facilitated by, but Does Not Require Cell-Associated CD4 J. Immunol., April 15, 2007; 178(8): 4846 - 4853. [Abstract] [Full Text] [PDF] G. Mangino, Z. A. Percario, G. Fiorucci, G. Vaccari, S. Manrique, G. Romeo, M. Federico, M. Geyer, and E. Affabris In Vitro Treatment of Human Monocytes/Macrophages with Myristoylated Recombinant Nef of Human Immunodeficiency Virus Type 1 Leads to the Activation of Mitogen-Activated Protein Kinases, I{kappa}B Kinases, and Interferon Regulatory Factor 3 and to the Release of Beta Interferon J. Virol., March 15, 2007; 81(6): 2777 - 2791. [Abstract] [Full Text] [PDF]

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