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Blood, 15 April 2005, Vol. 105, No. 8, pp. 3230-3237. Prepublished online as a Blood First Edition Paper on December 30, 2004; DOI 10.1182/blood-2004-06-2084. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-06-2084v1 105/8/3230    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 Suzu, S. Articles by Okada, S. Search for Related Content PubMed PubMed Citation Articles by Suzu, S. Articles by Okada, S. Related Collections Hematopoiesis and Stem Cells Immunobiology Phagocytes Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY HIV-1 Nef interferes with M-CSF receptor signaling through Hck activation and inhibits M-CSF bioactivities Shinya Suzu, Hideki Harada, Takahiro Matsumoto, and Seiji Okada From the Division of Hematopoiesis, Center for AIDS Research, Kumamoto University, Japan. HIV-1 Nef protein is a major determinant of the pathogenicity of the virus. It has been shown that Nef activates Hck, a member of Src family kinase, in monocytes/macrophages and that the interaction is critical for AIDS-like disease progression in a mouse model. However, it was unclear how the molecular interaction in monocytes/macrophages leads to disease progression. Here, we show for the first time that Nef interferes with the macrophage colony-stimulating factor (M-CSF)/M-CSF receptor signal pathway. In this study, we introduced a conditionally active Nef into myeloid leukemia TF-1-fms cells and analyzed their responsiveness to M-CSF. We found that Nef-activated Hck constitutively associated with the M-CSF receptor complex. The formation of the molecular complex should occur under physiologic conditions, that is, on M-CSF stimulation. Because of aberrant molecular association, the tyrosine-phosphorylation/activation of the receptor in response to M-CSF was markedly diminished in Nef-active cells. Consequently, Nef activation caused the inhibition of M-CSF-mediated proliferation of TF-1-fms cells and macrophage differentiation of the cells induced by M-CSF and 12-O-tetradecanoylphorbol 13-acetate. These results indicate that HIV-1 Nef interferes with M-CSF receptor signaling through Hck activation and thereby inhibits M-CSF functions in monocytes/macrophages. (Blood. 2005;105:3230-3237) CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M. Hiyoshi, S. Suzu, Y. Yoshidomi, R. Hassan, H. Harada, N. Sakashita, H. Akari, K. Motoyoshi, and S. Okada Interaction between Hck and HIV-1 Nef negatively regulates cell surface expression of M-CSF receptor Blood, January 1, 2008; 111(1): 243 - 250. [Abstract] [Full Text] [PDF] S. Suzu, M. Hiyoshi, H. Harada, and S. Okada HIV-1 Nef Inhibits M-CSF Signals by Down-Regulating Its Receptor Fms through Hck. Blood (ASH Annual Meeting Abstracts), November 16, 2006; 108(11): 1251 - 1251. [Abstract] [PDF] A. Pugliese, V. Vidotto, T. Beltramo, and D. Torre Phagocytic Activity in Human Immunodeficiency Virus Type 1 Infection Clin. Vaccine Immunol., August 1, 2005; 12(8): 889 - 895. [Full Text] [PDF]

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