DC-SIGN increases the affinity of HIV-1 envelope glycoprotein interaction with CD4.

Mannose-binding C-type lectin receptors, expressed on Langerhans cells and subepithelial dendritic cells (DCs) of cervico-vaginal tissues, play an important role in HIV-1 capture and subsequent dissemination to lymph nodes. DC-SIGN has been implicated in both productive infection of DCs and the DC-m...

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Main Authors: Karolin Hijazi, Yufei Wang, Carlo Scala, Simon Jeffs, Colin Longstaff, Daniel Stieh, Beth Haggarty, Guido Vanham, Dominique Schols, Jan Balzarini, Ian M Jones, James Hoxie, Robin Shattock, Charles G Kelly
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2011-01-01
Series:PLoS ONE
Online Access:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0028307&type=printable
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author Karolin Hijazi
Yufei Wang
Carlo Scala
Simon Jeffs
Colin Longstaff
Daniel Stieh
Beth Haggarty
Guido Vanham
Dominique Schols
Jan Balzarini
Ian M Jones
James Hoxie
Robin Shattock
Charles G Kelly
author_facet Karolin Hijazi
Yufei Wang
Carlo Scala
Simon Jeffs
Colin Longstaff
Daniel Stieh
Beth Haggarty
Guido Vanham
Dominique Schols
Jan Balzarini
Ian M Jones
James Hoxie
Robin Shattock
Charles G Kelly
author_sort Karolin Hijazi
collection DOAJ
description Mannose-binding C-type lectin receptors, expressed on Langerhans cells and subepithelial dendritic cells (DCs) of cervico-vaginal tissues, play an important role in HIV-1 capture and subsequent dissemination to lymph nodes. DC-SIGN has been implicated in both productive infection of DCs and the DC-mediated trans infection of CD4(+) T cells that occurs in the absence of replication. However, the molecular events that underlie this efficient transmission have not been fully defined. In this study, we have examined the effect of the extracellular domains of DC-SIGN and Langerin on the stability of the interaction of the HIV-1 envelope glycoprotein with CD4 and also on replication in permissive cells. Surface plasmon resonance analysis showed that DC-SIGN increases the binding affinity of trimeric gp140 envelope glycoproteins to CD4. In contrast, Langerin had no effect on the stability of the gp140:CD4 complex. In vitro infection experiments to compare DC-SIGN enhancement of CD4-dependent and CD4-independent strains demonstrated significantly lower enhancement of the CD4-independent strain. In addition DC-SIGN increased the relative rate of infection of the CD4-dependent strain but had no effect on the CD4-independent strain. DC-SIGN binding to the HIV envelope protein effectively increases exposure of the CD4 binding site, which in turn contributes to enhancement of infection.
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institution Kabale University
issn 1932-6203
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spelling doaj-art-6ffdc28f18324ddeb324bcee8e41573b2025-08-20T03:25:07ZengPublic Library of Science (PLoS)PLoS ONE1932-62032011-01-01612e2830710.1371/journal.pone.0028307DC-SIGN increases the affinity of HIV-1 envelope glycoprotein interaction with CD4.Karolin HijaziYufei WangCarlo ScalaSimon JeffsColin LongstaffDaniel StiehBeth HaggartyGuido VanhamDominique ScholsJan BalzariniIan M JonesJames HoxieRobin ShattockCharles G KellyMannose-binding C-type lectin receptors, expressed on Langerhans cells and subepithelial dendritic cells (DCs) of cervico-vaginal tissues, play an important role in HIV-1 capture and subsequent dissemination to lymph nodes. DC-SIGN has been implicated in both productive infection of DCs and the DC-mediated trans infection of CD4(+) T cells that occurs in the absence of replication. However, the molecular events that underlie this efficient transmission have not been fully defined. In this study, we have examined the effect of the extracellular domains of DC-SIGN and Langerin on the stability of the interaction of the HIV-1 envelope glycoprotein with CD4 and also on replication in permissive cells. Surface plasmon resonance analysis showed that DC-SIGN increases the binding affinity of trimeric gp140 envelope glycoproteins to CD4. In contrast, Langerin had no effect on the stability of the gp140:CD4 complex. In vitro infection experiments to compare DC-SIGN enhancement of CD4-dependent and CD4-independent strains demonstrated significantly lower enhancement of the CD4-independent strain. In addition DC-SIGN increased the relative rate of infection of the CD4-dependent strain but had no effect on the CD4-independent strain. DC-SIGN binding to the HIV envelope protein effectively increases exposure of the CD4 binding site, which in turn contributes to enhancement of infection.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0028307&type=printable
spellingShingle Karolin Hijazi
Yufei Wang
Carlo Scala
Simon Jeffs
Colin Longstaff
Daniel Stieh
Beth Haggarty
Guido Vanham
Dominique Schols
Jan Balzarini
Ian M Jones
James Hoxie
Robin Shattock
Charles G Kelly
DC-SIGN increases the affinity of HIV-1 envelope glycoprotein interaction with CD4.
PLoS ONE
title DC-SIGN increases the affinity of HIV-1 envelope glycoprotein interaction with CD4.
title_full DC-SIGN increases the affinity of HIV-1 envelope glycoprotein interaction with CD4.
title_fullStr DC-SIGN increases the affinity of HIV-1 envelope glycoprotein interaction with CD4.
title_full_unstemmed DC-SIGN increases the affinity of HIV-1 envelope glycoprotein interaction with CD4.
title_short DC-SIGN increases the affinity of HIV-1 envelope glycoprotein interaction with CD4.
title_sort dc sign increases the affinity of hiv 1 envelope glycoprotein interaction with cd4
url https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0028307&type=printable
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