Human epithelial beta-defensins 2 and 3 inhibit HIV-1 replication - PubMed (original) (raw)
. 2003 Nov 7;17(16):F39-48.
doi: 10.1097/00002030-200311070-00001.
Michael M Lederman, Zhimin Feng, Bikram Chakraborty, Jan Weber, Hector R Rangel, Michael L Marotta, Muneer Mirza, Bin Jiang, Patti Kiser, Kathy Medvik, Scott F Sieg, Aaron Weinberg
Affiliations
- PMID: 14571200
- DOI: 10.1097/00002030-200311070-00001
Human epithelial beta-defensins 2 and 3 inhibit HIV-1 replication
Miguel E Quiñones-Mateu et al. AIDS. 2003.
Abstract
Objective: Mechanisms underlying mucosal transmission of HIV-1 are incompletely understood. We describe the anti-HIV-1 activity of human beta-defensins (hBD), small cationic molecules that provide protection at mucosal surfaces.
Methods and results: HIV-1 induced expression of hBD-2 and -3 mRNA (but not that of hBD-1) 4- to 78-fold, respectively, above baseline in normal human oral epithelial cells. HIV-1 failed to infect these cells, even after 5 days of exposure. Recombinant hBD-1 had no antiviral activity, while rhBD-2 and rhBD-3 showed concentration-dependent inhibition of HIV-1 replication without cellular toxicity. Inhibition was greater against CXCR4-tropic than against the CCR5-tropic HIV-1 isolates. hBD-2 and hBD-3 induced an irreversible effect on virion infectivity, with electron microscopy confirming binding of hBDs to viral particles. Finally, hBD-2 and -3 induced downmodulation of the HIV-1 coreceptor CXCR4 (but not CCR5) in peripheral blood mononuclear cells and T lymphocytic cells as shown by confocal microscopy and flow cytometry.
Conclusions: This study shows for the first time that HIV-1 induces beta-defensin expression in human oral epithelial cells and that beta-defensins block HIV-1 replication via a direct interaction with virions and through modulation of the CXCR4 coreceptor. These properties may be exploited as strategies for mucosal protection against HIV-1 transmission.
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