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Blood, 15 November 2006, Vol. 108, No. 10, pp. 3305-3312. Prepublished online as a Blood First Edition Paper on July 20, 2006; DOI 10.1182/blood-2006-04-014829. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2006-04-014829v1 108/10/3305    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 Yamamoto, T. Articles by Tsunetsugu-Yokota, Y. Search for Related Content PubMed PubMed Citation Articles by Yamamoto, T. Articles by Tsunetsugu-Yokota, Y. Related Collections Immunobiology Phagocytes Gene Therapy Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  GENE THERAPY Lentivirus vectors expressing short hairpin RNAs against the U3-overlapping region of HIV nef inhibit HIV replication and infectivity in primary macrophages Takuya Yamamoto, Hiroyuki Miyoshi, Norio Yamamoto, Naoki Yamamoto, Jun-ichiro Inoue, and Yasuko Tsunetsugu-Yokota From the Department of Immunology, National Institute of Infectious Diseases, Toyama, Shinjuku-ku, Tokyo; Subteam for Manipulation of Cell Fate, BioResource Center, RIKEN Tsukuba Institute, Tsukuba; Department of Molecular Virology, Bio-Response, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo; AIDS Research Center, National Institute of Infectious Diseases, Shinjuku, Tokyo; and Division of Cellular and Molecular Biology, Department of Cancer Biology, Institute of Medical Science, University of Tokyo, Shirokane-dai, Minato-ku, Tokyo, Japan. Although successful attempts to inhibit HIV-1 replication in T cells using RNAi have been reported, the effect of HIV-specific RNAi on macrophages is not well known. Macrophages are key targets for anti–HIV-1 therapy because they are able to survive long after the initial infection with HIV and can spread the virus to T cells. In this study, we identified a putative RNAi target of HIV, consisting of the portion of the nef gene overlapping the U3 region (Nef366), and generated a lentivirus-based short hairpin RNA (shRNA) expression vector (Lenti shNef366). We show that Lenti shNef366 inhibits (1) HIV-1 replication in a monocytic cell line and in primary monocyte-derived macrophages (MDMs), (2) reactivation of latent HIV-1 infection, and (3) the production of secondary HIV-1 from MDMs harboring a genomic copy of Nef366. Moreover, we found that the up-regulated production of macrophage inflammatory protein 1 (MIP-1), but not MIP-1, in MDMs by Nef expression was considerably suppressed by Lenti shNef366, which suggests that HIV-1 dissemination to T cells through its interaction with HIV-1–infected MDMs can also be controlled by Lenti shNef366. Thus, lentivirus-mediated shRNA expression targeting the U3-overlapping region of HIV nef represents a feasible approach to genetic vaccine therapy for HIV-1. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: H. Watarai, E. Sekine, S. Inoue, R. Nakagawa, T. Kaisho, and M. Taniguchi PDC-TREM, a plasmacytoid dendritic cell-specific receptor, is responsible for augmented production of type I interferon PNAS, February 26, 2008; 105(8): 2993 - 2998. [Abstract] [Full Text] [PDF]

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