α-defensins block the early steps of HIV-1 infection: Interference with the binding of gp120 to CD4

Lucinda Furci, Francesca Sironi, Monica Tolazzi, Lia Vassena, Paolo Lusso

Research output: Contribution to journalArticle

77 Citations (Scopus)

Abstract

α-defensins are antibiotic peptides that act as natural inhibitors of HIV-1 infection. However, the mechanisms of such inhibition are still unclear. Here we demonstrate that α-defensins block the earliest steps in the viral infectious cycle, as documented using an HIV-1 envelope-mediated cell-fusion assay. A broad-spectrum inhibitory activity was observed on primary and laboratory-adapted HIV-1 isolates irrespective of their coreceptor specificity and genetic subtype. A primary mechanism of such inhibition was identified as the ability of α-defensins to bind specifically both to the primary HIV-1 cellular receptor, CD4, and to the viral envelope glycoprotein, gp120. Moreover, treatment of CD4+ T cells with α-defensins caused a dramatic downmodulation of CD4 expression. By monoclonal antibody competition, the regions of interaction with α-defensins were mapped to the D1 domain of CD4 and to a surface contiguous to the CD4- and coreceptor-binding sites of gp120. Consistent with these findings, α-defensins inhibited the binding of gp120 to CD4. These data demonstrate that α-defensins specifically block the initial phase of the HIV infectious cycle and modulate the expression of CD4, a critical receptor in the physiology of T-cell activation.

Original languageEnglish
Pages (from-to)2928-2935
Number of pages8
JournalBlood
Volume109
Issue number7
DOIs
Publication statusPublished - Apr 1 2007

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Defensins
HIV Infections
HIV-1
T-cells
T-Lymphocytes
CD4 Antigens
Cell Fusion
Physiology
Assays
Glycoproteins
Fusion reactions
Chemical activation
Binding Sites
Monoclonal Antibodies
HIV
Anti-Bacterial Agents
Peptides

ASJC Scopus subject areas

  • Hematology

Cite this

α-defensins block the early steps of HIV-1 infection : Interference with the binding of gp120 to CD4. / Furci, Lucinda; Sironi, Francesca; Tolazzi, Monica; Vassena, Lia; Lusso, Paolo.

In: Blood, Vol. 109, No. 7, 01.04.2007, p. 2928-2935.

Research output: Contribution to journalArticle

Furci, Lucinda ; Sironi, Francesca ; Tolazzi, Monica ; Vassena, Lia ; Lusso, Paolo. / α-defensins block the early steps of HIV-1 infection : Interference with the binding of gp120 to CD4. In: Blood. 2007 ; Vol. 109, No. 7. pp. 2928-2935.
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