Human epithelial β-defensins 2 and 3 inhibit HIV-1 replication

Abstract

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.

Extracellular HIV-1 Tat Induces Human Beta-Defensin-2 Production Via NF-kappaB/AP-1 Dependent Pathways in Human B Cells

“…Antimicrobial peptides such as defensins serve to combat bacterial and viral infection. Human beta-defensins (hBD) such as hBD-2 have been shown to exert anti-HIV activity (Quiñones-Mateu et al, 2003;Sun et al, 2005;Weinberg et al, 2006). hBD is upregulated in various cell types in response to bacterial infection and pro-inflammatory cytokines (Tsutsumi-Ishii et al, 2000;Wehkamp et al, 2006).…”

“…It has been demonstrated that human oral epithelial cells expressed hBD-2 and 3 mRNA upon stimulation with HIV-1 virions (Quiñones-Mateu et al, 2003). We hypothesized that besides the HIV-1 virion, viral proteins such as HIV-1 Tat may contribute to up-regulate expression of hBD.…”

“…Previous studies have demonstrated that a class of defensins was an effective inhibitor of HIV-1 infection in vitro and in vivo (for review, see Cole and Lehrer, 2003). Human beta-defensins (hBD), such as hBD-2, have been shown to exert anti-HIV activity (Quiñones-Mateu et al, 2003;Sun et al, 2005;Weinberg et al, 2006). It has been demonstrated that hBD-2 and 3 expressed in human oral epithelial cells inhibited HIV-1 replication via a direct interaction with virions and through modulation of the CXCR4 coreceptor (Quiñones-Mateu et al, 2003;Weinberg et al, 2006).…”

“…Human beta-defensins (hBD), such as hBD-2, have been shown to exert anti-HIV activity (Quiñones-Mateu et al, 2003;Sun et al, 2005;Weinberg et al, 2006). It has been demonstrated that hBD-2 and 3 expressed in human oral epithelial cells inhibited HIV-1 replication via a direct interaction with virions and through modulation of the CXCR4 coreceptor (Quiñones-Mateu et al, 2003;Weinberg et al, 2006). In addition to exerting direct antiviral effects against HIV-1, defensins have immune-stimulatory activity because they mediate the signals involved in adaptive immune responses (Bowdish et al, 2006).…”

“…hBD is up-regulated in various cell types in response to microbial infection and pro-inflammatory cytokines (TsutsumiIshii et al, 2000;Wehkamp et al, 2006). Previous studies have shown that HIV-1 virion can induce the expression of hBD, even in the absence of HIV-1 replication (Quiñones-Mateu et al, 2003). However, little is known about the molecular mechanisms by which HIV-1 induces the expression of hBD.…”