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 language | English |
|---|---|
| Pages (from-to) | 2928-2935 |
| Number of pages | 8 |
| Journal | Blood |
| Volume | 109 |
| Issue number | 7 |
| DOIs | |
| Publication status | Published - Apr 1 2007 |
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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 journal › Article
}
TY - JOUR
T1 - α-defensins block the early steps of HIV-1 infection
T2 - Interference with the binding of gp120 to CD4
AU - Furci, Lucinda
AU - Sironi, Francesca
AU - Tolazzi, Monica
AU - Vassena, Lia
AU - Lusso, Paolo
PY - 2007/4/1
Y1 - 2007/4/1
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=33947579340&partnerID=8YFLogxK
U2 - 10.1182/blood-2006-05-024489
DO - 10.1182/blood-2006-05-024489
M3 - Article
C2 - 17132727
AN - SCOPUS:33947579340
VL - 109
SP - 2928
EP - 2935
JO - Blood
JF - Blood
SN - 0006-4971
IS - 7
ER -