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Blood, 15 February 2004, Vol. 103, No. 4, pp. 1211-1217. Prepublished online as a Blood First Edition Paper on October 23, 2003; DOI 10.1182/blood-2003-08-2669. This Article Full Text Full Text (PDF) All Versions of this Article: 2003-08-2669v1 103/4/1211    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 CrossRef Citing Articles via Google Scholar Google Scholar Articles by Agrawal, L. Articles by Alkhatib, G. Search for Related Content PubMed PubMed Citation Articles by Agrawal, L. Articles by Alkhatib, G. Related Collections Immunobiology Chemokines, Cytokines, and Interleukins Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  CHEMOKINES Specific inhibition of HIV-1 coreceptor activity by synthetic peptides corresponding to the predicted extracellular loops of CCR5 Lokesh Agrawal, Zainab VanHorn-Ali, Edward A. Berger, and Ghalib Alkhatib From the Department of Microbiology and Immunology and the Walther Cancer Institute, Indiana University School of Medicine, Indianapolis, IN; and the Laboratory of Viral Diseases, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD. We used synthetic peptides to the extracellular loops (ECLs) of CCR5 to examine inhibitory effects on HIV infection/fusion with primary leukocytes and cells expressing recombinant CCR5. We show for the first time that peptides derived from the first, second, or third ECL caused dose-dependent inhibition of fusion and infection, although with varying potencies and specificities for envelope glycoproteins (Envs) from different strains. The first and third ECL peptides inhibited Envs from the R5 Ba-L strain and the R5X4 89.6 strain, whereas the second ECL peptide inhibited Ba-L but not 89.6 Env. None of the peptides affected fusion mediated by Env from the X4 LAV strain. Fusion mediated by Envs from several primary HIV-1 isolates was also inhibited by the peptides. These findings suggest that various HIV-1 strains use CCR5 domains in different ways. Experiments involving peptide pretreatment and washing, modulation of the expression levels of Env and CCR5, analysis of CCR5 peptide effects against different coreceptors, and inhibition of radiolabeled glycoprotein (gp) 120 binding to CCR5 suggested that the peptide-blocking activities reflect their interactions with gp120. The CCR5-derived ECL peptides thus provide a useful approach to analyze structure–function relationships involved in HIV-1 Env-coreceptor interactions and may have implications for the design of drugs that inhibit HIV infection. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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