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

K Hijazi, Y Wang, C Scala, S Jeffs, C Longstaff, D Stieh, B Haggarty, G Vanham, D Schols, J Balzarini, IM Jones, J Hoxie, R Shattock, CG Kelly

    Research output: Contribution to journalA1: Web of Science-article

    Abstract

    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
    JournalPLoS ONE
    Volume6
    Issue number12
    Pages (from-to)e28307
    Number of pages14
    ISSN1932-6203
    DOIs
    Publication statusPublished - 2011

    Keywords

    • B780-tropical-medicine
    • Viral diseases
    • HIV-1
    • AIDS
    • Lymph nodes
    • Lectins-C-Type
    • Langerhans cells
    • Dendritic cells
    • CD4
    • Molecular
    • Disease transmission
    • GP140
    • Envelope proteins
    • Glycoproteins
    • In vitro
    • Strains
    • Laboratory techniques and procedures

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