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

Jian Ding, Aprille Rapista, Natalia Teleshova, Wuyuan Lu, Mary E. Klotman, Theresa L. Chang

Research output: Contribution to journalArticle

14 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)208-212
Number of pages5
JournalJournal of Innate Immunity
Volume3
Issue number2
DOIs
StatePublished - Feb 1 2011
Externally publishedYes

Fingerprint

Defensins
Anti-Infective Agents
HIV
Carrageenan
Local Anti-Infective Agents
HIV Infections
Mucous Membrane
Epithelial Cells
polyanions
Clinical Trials
Peptides

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy

Keywords

  • Defensins
  • HIV
  • Polyanion microbicides

Cite this

Ding, Jian ; Rapista, Aprille ; Teleshova, Natalia ; Lu, Wuyuan ; Klotman, Mary E. ; Chang, Theresa L. / Mucosal human defensins 5 and 6 antagonize the anti-HIV activity of candidate polyanion microbicides. In: Journal of Innate Immunity. 2011 ; Vol. 3, No. 2. pp. 208-212.
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Mucosal human defensins 5 and 6 antagonize the anti-HIV activity of candidate polyanion microbicides. / Ding, Jian; Rapista, Aprille; Teleshova, Natalia; Lu, Wuyuan; Klotman, Mary E.; Chang, Theresa L.

In: Journal of Innate Immunity, Vol. 3, No. 2, 01.02.2011, p. 208-212.

Research output: Contribution to journalArticle

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AU - Ding, Jian

AU - Rapista, Aprille

AU - Teleshova, Natalia

AU - Lu, Wuyuan

AU - Klotman, Mary E.

AU - Chang, Theresa L.

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