Mucosal human defensins 5 and 6 antagonize the anti-HIV activity of candidate polyanion microbicides.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Ding, J; Rapista, A; Teleshova, N; Lu, W; Klotman, ME; Chang, TL

Published Date

  • 2011

Published In

Volume / Issue

  • 3 / 2

Start / End Page

  • 208 - 212

PubMed ID

  • 21160168

Pubmed Central ID

  • 21160168

Electronic International Standard Serial Number (EISSN)

  • 1662-8128

Digital Object Identifier (DOI)

  • 10.1159/000322355

Language

  • eng

Conference Location

  • Switzerland