title: Mucosal human defensins 5 and 6 antagonize the anti-HIV activity of candidate polyanion microbicides.
abstract: 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.
authors.affiliation: Public Health Research Institute, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark, NJ 07103, USA.
authors.forename: Jian
authors.initials: J
authors.lastname: Ding
authors.forename: Aprille
authors.initials: A
authors.lastname: Rapista
authors.forename: Natalia
authors.initials: N
authors.lastname: Teleshova
authors.forename: Wuyuan
authors.initials: W
authors.lastname: Lu
authors.forename: Mary E
authors.initials: ME
authors.lastname: Klotman
authors.forename: Theresa L
authors.initials: TL
authors.lastname: Chang
mesh_terms: D019380:Anti-HIV Agents / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000494:pharmacology; D000890:Anti-Infective Agents / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000494:pharmacology; D015496:CD4-Positive T-Lymphocytes; D002351:Carrageenan / Q000494:pharmacology; D002482:Cellulose / Q000031:analogs & derivatives / Q000494:pharmacology; D023082:Defensins / Q000276:immunology / Q000378:metabolism* / Q000494:pharmacology; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000821:virology; D015497:HIV-1 / Q000187:drug effects* / Q000472:pathogenicity*; D006367:HeLa Cells; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology; D009092:Mucous Membrane / Q000276:immunology*; D009282:Naphthalenesulfonates / Q000494:pharmacology; D000071228:Polyelectrolytes; D011108:Polymers / Q000494:pharmacology*; D014621:Vagina / Q000276:immunology
chemical_list: D019380:Anti-HIV Agents; D000890:Anti-Infective Agents; D002351:Carrageenan; D002482:Cellulose; D023082:Defensins; D009282:Naphthalenesulfonates; D000071228:Polyelectrolytes; D011108:Polymers; C120231:PRO 2000; C020254:cellulose sulfate