SEARCH:   Advanced

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 (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 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. A Search for Related Content PubMed PubMed Citation Articles by Agrawal, L. Articles by Alkhatib, G. A Social Bookmarking                   What's this? Submitted August 12, 2003 Accepted October 16, 2003 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 A Alkhatib* Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN, USA Laboratory of Viral Diseases, National Institutes of Health, Bethesda, MD, USA * Corresponding author; email: galkhati{at}iupui.edu. We utilized synthetic peptides to the extracellular loops (ECL) 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 Envs from different strains. The first and third ECL peptides inhibited Envs from both 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 pre-treatment and washing, modulation of the expression levels of Env and CCR5, analysis of CCR5 peptide effects against different coreceptors, and inhibition of radiolabeled gp120 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?

	Copyright © 2003 by American Society of Hematology         Online ISSN: 1528-0020