V3 loop-derived peptide SPC3 inhibits infection of CD4- and galactosylceramide- cells by LAV-2/B.
SPC3, a synthetic multibranched peptide including the GPGRAF consensus motif of the human immunodeficiency virus type 1 (HIV-1) gp120 V3-loop is a potent inhibitor of HIV infection of human CD4+ lymphocytes, macrophages and CD4-/galactosylceramide+ human colon epithelial cells and is currently tested in phase II clinical trials (FDA protocol 257 A). The antiviral property of SPC3 was further investigated for its ability to inhibit LAV-2/B, an HIV-2 clone with a CD4-independent tropism. SPC3 inhibited the LAV-2/B-mediated infection of B-cell line which does not express the CD4 and the galactosylceramide molecules on their cell surface, suggesting an SPC3-sensitive CD4/galactosylceramide-independent pathway of viral infection in HIV susceptible cells. The molecular mechanism of the peptide inhibition was also investigated. The data suggested that the SPC3-mediated inhibition does not result from a direct competition between SPC3 and gp120 binding to the cell surface of the target cell.
Centre d'Immunologie de Marseille Luminy, France. mmoulard@scripps.edu
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Moulard
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Mabrouk
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Martin
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Van Rietschoten
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Rochat
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Sabatier
D000595:Amino Acid Sequence; D000998:Antiviral Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D001667:Binding, Competitive; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D002459:Cell Fusion / Q000187:drug effects; D002460:Cell Line / Q000187:drug effects / Q000378:metabolism / Q000821:virology; D003106:Colon / Q000166:cytology / Q000187:drug effects / Q000821:virology; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism / Q000821:virology; D005699:Galactosylceramides / Q000378:metabolism*; D015699:HIV Envelope Protein gp120 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D015658:HIV Infections / Q000188:drug therapy; D015498:HIV-2 / Q000187:drug effects* / Q000472:pathogenicity; D006801:Humans; D008969:Molecular Sequence Data; D019713:Receptors, CCR5 / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism
D000998:Antiviral Agents; D005699:Galactosylceramides; D015699:HIV Envelope Protein gp120; D019713:Receptors, CCR5; D019718:Receptors, CXCR4; D011994:Recombinant Proteins; C098257:SPC3 peptide