Differential activity of candidate microbicides against early steps of HIV-1 infection upon complement virus opsonization

MA Jenabian, H Saidi, C Charpentier, H Bouhlal, D Schols, J Balzarini, TW Bell, G Vanham, L Belec

    Research output: Contribution to journalA4: Article in journal not included in A1, A2 or A3

    Abstract

    BACKGROUND: HIV-1 in genital secretions may be opsonized by several molecules including complement components. Opsonized HIV-1 by complement enhances the infection of various mucosal target cells, such as dendritic cells (DC) and epithelial cells. RESULTS: We herein evaluated the effect of HIV-1 complement opsonization on microbicide candidates activity, by using three in vitro mucosal models: CCR5-tropic HIV-1JR-CSF transcytosis through epithelial cells, HIV-1JR-CSF attachment on immature monocyte-derived dendritic cells (iMDDC), and infectivity of iMDDC by CCR5-tropic HIV-1BaL and CXCR4-tropic HIV-1NDK. A panel of 10 microbicide candidates [T20, CADA, lectines HHA & GNA, PVAS, human lactoferrin, and monoclonal antibodies IgG1B12, 12G5, 2G12 and 2F5], were investigated using cell-free unopsonized or opsonized HIV-1 by complements. Only HHA and PVAS were able to inhibit HIV trancytosis. Upon opsonization, transcytosis was affected only by HHA, HIV-1 adsorption on iMDDC by four molecules (lactoferrin, IgG1B12, IgG2G5, IgG2G12), and replication in iMDDC of HIV-1BaL by five molecules (lactoferrin, CADA, T20, IgG1B12, IgG2F5) and of HIV-1NDK by two molecules (lactoferrin, IgG12G5). CONCLUSION: These observations demonstrate that HIV-1 opsonization by complements may modulate in vitro the efficiency of candidate microbicides to inhibit HIV-1 infection of mucosal target cells, as well as its crossing through mucosa.
    Original languageEnglish
    JournalAIDS Research and Therapy
    Volume7
    Pages (from-to)16
    Number of pages8
    ISSN1742-6405
    DOIs
    Publication statusPublished - 2010

    Keywords

    • B780-tropical-medicine
    • Viral diseases
    • HIV-1
    • AIDS
    • Evaluation
    • Mucosal
    • Models
    • In vitro
    • Microbicides
    • Opsonization
    • Epithelial cells
    • Dendritic cells
    • CCR5
    • CXCR4
    • Complement

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