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.