HSV Neutralization by the Microbicidal Candidate C5A

PLoS One

Philippe A. Gallay¹  Michael D. Bobardt¹  Udayan Chatterji¹  Georges M. G. M. Verjans²  Freek B. van Loenen²  Teunis B. H. Geijtenbeek³  Lot de Witte³ 

[1] Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, California, United States of America;Department of Virology, Erasmus Medical Centre, Rotterdam, The Netherlands;The Center for Experimental and Molecular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

关键词: HIV-1;    Viral packaging;    Cell membranes;    Epithelial cells;    Viral structure;    Vero cells;    Vesicular stomatitis virus;    Herpes simplex virus;   

DOI  :  10.1371/journal.pone.0018917

学科分类：医学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY