title: HSV neutralization by the microbicidal candidate C5A.
abstract: Genital herpes is a major risk factor in acquiring human immunodeficiency virus type-1 (HIV-1) infection and is caused by both Herpes Simplex virus type 1 (HSV-1) and HSV-2. The amphipathic peptide C5A, derived from the non-structural hepatitis C virus (HCV) protein 5A, was shown to prevent HIV-1 infection but neither influenza nor vesicular stomatitis virus infections. Here we investigated the antiviral function of C5A on HSV infections. C5A efficiently inhibited both HSV-1 and HSV-2 infection in epithelial cells in vitro as well as in an ex vivo epidermal infection model. C5A destabilized the integrity of the viral HSV membrane. Furthermore, drug resistant HSV strains were inhibited by this peptide. Notably, C5A-mediated neutralization of HSV-1 prevented HIV-1 transmission. An in vitro HIV-1 transmigration assay was developed using primary genital epithelial cells and HSV infection increased HIV-1 transmigration. Treatment with C5A abolished HIV-1 transmigration by preventing HSV infection and by preserving the integrity of the genital epithelium that was severely compromised by HSV infection. In conclusion, this study demonstrates that C5A represents a multipurpose microbicide candidate, which neutralizes both HIV-1 and HSV, and which may interfere with HIV-1 transmission through the genital epithelium.
authors.affiliation: The Center for Experimental and Molecular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Lot
authors.initials: L
authors.lastname: de Witte
authors.forename: Michael D
authors.initials: MD
authors.lastname: Bobardt
authors.forename: Udayan
authors.initials: U
authors.lastname: Chatterji
authors.forename: Freek B
authors.initials: FB
authors.lastname: van Loenen
authors.forename: Georges M G M
authors.initials: GM
authors.lastname: Verjans
authors.forename: Teunis B H
authors.initials: TB
authors.lastname: Geijtenbeek
authors.forename: Philippe A
authors.initials: PA
authors.lastname: Gallay
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D015497:HIV-1 / Q000187:drug effects; D018259:Herpesvirus 1, Human / Q000187:drug effects*; D018258:Herpesvirus 2, Human / Q000187:drug effects*; D006801:Humans; D010455:Peptides / Q000494:pharmacology*; D014709:Vero Cells
chemical_list: D000998:Antiviral Agents; D010455:Peptides