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Blood, 1 November 2003, Vol. 102, No. 9, pp. 3280-3286. Prepublished online as a Blood First Edition Paper on July 10, 2003; DOI 10.1182/blood-2003-04-1096. This Article Full Text Full Text (PDF) All Versions of this Article: 2003-04-1096v1 102/9/3280    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 Golding, H. Articles by Sher, A. Search for Related Content PubMed PubMed Citation Articles by Golding, H. Articles by Sher, A. Related Collections Chemokines, Cytokines, and Interleukins Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Inhibition of HIV-1 infection by a CCR5-binding cyclophilin from Toxoplasma gondii Hana Golding, Julio Aliberti, Lisa R. King, Jody Manischewitz, John Andersen, Jesus Valenzuela, Nathaniel R. Landau, and Alan Sher From the Division of Viral Products, Center for Biologics Evaluation and Research (CBER), Food and Drug Administration, Bethesda, MD; the Laboratory of Parasitic Diseases and the Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), Bethesda, MD; and the Salk Institute for Biological Studies, Infectious Diseases Laboratory, La Jolla, CA. The activation of murine dendritic cells by Toxoplasma gondii has recently been shown to depend on a parasite protein that signals through the chemokine receptor CCR5. Here we demonstrate that this molecule, cyclophilin-18 (C-18), is an inhibitor of HIV-1 cell fusion and infection with cell-free virus. T gondii C-18 efficiently blocked syncytium formation between human T cells and effector cells expressing R5 but not X4 envelopes. Neither human nor Plasmodium falciparum cyclophilins possess such inhibitory activity. Importantly, C-18 protected peripheral blood leukocytes from infection with multiple HIV-1 R5 primary isolates from several clades. C-18 bound directly to human CCR5, and this interaction was partially competed by the -chemokine macrophage inflammatory protein 1 (MIP-1) and by HIV-1 R5 gp120. In contrast to several other antagonists of HIV coreceptor function, C-18 mediated inhibition did not induce -chemokines or cause CCR5 downmodulation, suggesting direct blocking of envelope binding to the receptor. These data support the further development of C-18 derivatives as HIV-1 inhibitors for preventing HIV-1 transmission and for postexposure prophylaxis. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: S. Bhatnagar, K. Shinagawa, F. J. Castellino, and J. S. Schorey Exosomes released from macrophages infected with intracellular pathogens stimulate a proinflammatory response in vitro and in vivo Blood, November 1, 2007; 110(9): 3234 - 3244. [Abstract] [Full Text] [PDF] H. Golding, S. Khurana, F. Yarovinsky, L. R. King, G. Abdoulaeva, L. Antonsson, C. Owman, E. J. Platt, D. Kabat, J. F. Andersen, et al. CCR5 N-terminal Region Plays a Critical Role in HIV-1 Inhibition by Toxoplasma gondii-derived Cyclophilin-18 J. Biol. Chem., August 19, 2005; 280(33): 29570 - 29577. [Abstract] [Full Text] [PDF] F. Yarovinsky, J. F. Andersen, L. R. King, P. Caspar, J. Aliberti, H. Golding, and A. Sher Structural Determinants of the Anti-HIV Activity of a CCR5 Antagonist Derived from Toxoplasma gondii J. Biol. Chem., December 17, 2004; 279(51): 53635 - 53642. [Abstract] [Full Text] [PDF]

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