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

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

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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.
Original languageEnglish
Article numbere28307
Number of pages14
JournalPloS ONE
Issue number12
Publication statusPublished - 7 Dec 2011


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