Siglecs facilitate HIV-1 infection of macrophages through adhesion with viral sialic acids

Zhongcheng Zou, Ashley Chastain, Susan Moir, Jennifer Ford, Kathryn Trandem, Elena Martinelli, Claudia Cicala, Paul Crocker, James Arthos, Peter D. Sun

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    Abstract

    Background: Human immunodeficiency virus type 1 (HIV-1) infects macrophages effectively, despite relatively low levels of cell surface-expressed CD4. Although HIV-1 infections are defined by viral tropisms according to chemokine receptor usage (R5 and X4), variations in infection are common within both R5- and X4-tropic viruses, indicating additional factors may contribute to viral tropism.

    Methodology and Principal Findings: Using both solution and cell surface binding experiments, we showed that R5- and X4-tropic HIV-1 gp120 proteins recognized a family of I-type lectin receptors, the Sialic acid-binding immunoglobulin-like lectins (Siglec). The recognition was through envelope-associated sialic acids that promoted viral adhesion to macrophages. The sialic acid-mediated viral-host interaction facilitated both R5-tropic pseudovirus and HIV-1(BaL) infection of macrophages. The high affinity Siglec-1 contributed the most to HIV-1 infection and the variation in Siglec-1 expression on primary macrophages from different donors was associated statistically with sialic acid-facilitated viral infection. Furthermore, envelope-associated sialoglycan variations on various strains of R5-tropic viruses also affected infection.

    Conclusions and Significance of the Findings: Our study showed that sialic acids on the viral envelope facilitated HIV-1 infection of macrophages through interacting with Siglec receptors, and the expression of Siglec-1 correlated with viral sialic acid-mediated host attachment. This glycan-mediated viral adhesion underscores the importance of viral sialic acids in HIV infection and pathogenesis, and suggests a novel class of antiviral compounds targeting Siglec receptors.

    Original languageEnglish
    Article numbere24559
    Pages (from-to)-
    Number of pages15
    JournalPLoS ONE
    Volume6
    Issue number9
    DOIs
    Publication statusPublished - 8 Sep 2011

    Keywords

    • Human immunodeficiency virus
    • GP120 envelope glycoprotein
    • Myelin-associated glycoprotein
    • I-type lectins
    • Influenza hemagglutinin
    • Mannose receptor
    • Dendritic cells
    • B-lymphocytes
    • Type-1
    • Protein

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