AIDSWEEKLY Plus; Monday, February 9, 2009
Staff Medical Writers

NewsRx -- "The membrane proximal region (MPR) of the transmembrane subunit, gp41, of the HIV envelope glycoprotein plays a critical role in HIV-1 infection of CD4(+) target cells and CD4-independent mucosal entry. It contains continuous epitopes recognized by neutralizing IgG antibodies 2F5, 4E10 and Z13, and is therefore considered to be a promising target for vaccine design," researchers in Paris, France report (see also HIV/AIDS).

"Moreover, some MPR-derived peptides, such as T20 (enfuvirtide), are in clinical use as HIV-1 inhibitors. We have shown that an extended MPR peptide, P5, harbouring the lectin-like domain of gp41 and a calcium-binding site, is implicated in the interaction of HIV with its mucosal receptor. We now investigate the potential antiviral activities of P5 and other such long MPR-derived peptides. Structural studies of gp41 MPR-derived peptides using circular dichroism showed that the peptides P5 (a. a. 628-683), P1 (a.a.648-683), P5L (a.a.613-683) and P7 (a.a.613-746) displayed a well-defined alpha-helical structure. Peptides P5 inhibited HIV-1 envelope mediated cell-cell fusion and infection of peripheral blood mononuclear cells by both X4-and R5-tropic HIV-1 strains, whereas peptides P5 mutated in the calcium binding site or P1 lacked antiviral activity, when P5L blocked cell fusion in contrast to P7. Strikingly, P5 inhibited CD4-dependent infection by T20-resistant R5-tropic HIV-1 variants. Cell-cell fusion studies indicated that the anti-HIV-1 activity of P5, unlike T20, could not be abrogated in the presence of the N-terminal leucine zipper domain (LZ)," wrote H. Yu and colleagues, University of Paris.

The researchers concluded: "These results suggested that P5 could serve as a potent fusion inhibitor."

Yu and colleagues published their study in Retrovirology (Peptide P5 (Residues 628-683), comprising the entire membrane proximal region of HIV-1 gp41 and its calcium-binding site, is a potent inhibitor of HIV-1 infection. Retrovirology. 2008 Oct 16;5:93.

For additional information, contact M. Bomsel, University of Paris, CNRS UMR 8104, Dept. of Cell Biology, Institute Cochin, Muscosal Entry HIV & Mucosal Immun 1, 22 Rue Mechain, F-75014 Paris, France.

Publisher contact information for the journal Retrovirology is: Biomedical Central Ltd., Current Science Group, Middlesex House, 34-42 Cleveland St., London W1T 4LB, England.

Keywords: France, Paris, HIV/AIDS, AIDS, Acquired Immunodeficiency Syndrome, Antiviral, Biotechnology, Drugs, Enfuvirtide, Fusion Inhibitor, HIV, Human Immunodeficiency Virus, Peptide, Pharmaceuticals, Proteins, Proteomics, Retrovirology, Treatment, Vaccines, Viral Inhibition, Viral Therapy, Virology, University of Paris.

This article was prepared by AIDS Weekly editors from staff and other reports.

2009-02-09
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