Open AccessMucosal Human Defensins 5 and 6 Antagonize the Anti-HIV Activity of Candidate Polyanion Microbicides
Author(s) -
Jian Ding,
Aprille Rapista,
Natalia Teleshova,
Wuyuan Lu,
Mary E. Klotman,
Theresa L. Chang
Publication year - 2010
Publication title -
journal of innate immunity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.078
H-Index - 64
eISSN - 1662-8128
pISSN - 1662-811X
DOI - 10.1159/000322355
Subject(s) - microbicides for sexually transmitted diseases , infectivity , microbicide , in vitro , mucous membrane , human immunodeficiency virus (hiv) , chemistry , microbiology and biotechnology , biology , pharmacology , immunology , population , virus , medicine , biochemistry , environmental health , health services
Defensins are highly abundant antimicrobial peptides in the female genital mucosa. We have previously shown that human defensins 5 and 6 (HD5 and HD6), produced by cervicovaginal epithelial cells, significantly enhance HIV infectivity in vitro. Candidate polyanion microbicides, including PRO 2000, cellulose sulfate and carrageenan, failed to protect women against HIV infection in large-scale clinical trials, but the molecular basis of ineffectiveness was not clear. We hypothesized that mucosal host factors such as HD5 an HD6 may alter the activity of polyanion microbicides against HIV. Our results demonstrated that HD5 and HD6 but not their linear analogs antagonized the anti-HIV activity of PRO 2000, cellulose sulfate and carrageenan in vitro. Polyanion microbicides also reduced the HIV-enhancing effect of these defensins. We conclude that mucosal host factors could negatively impact the efficacy of topical microbicides against HIV, and their impact on the activity of candidate microbicides needs to be considered during the preclinical evaluation.