title: Differential activity of candidate microbicides against early steps of HIV-1 infection upon complement virus opsonization.
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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Université Paris Descartes (Paris V), Laboratoire de Virologie, Hôpital Européen Georges Pompidou, Paris, France. prbelecl@yahoo.fr.
authors.forename: Mohammad-Ali
authors.initials: MA
authors.lastname: Jenabian
authors.forename: Héla
authors.initials: H
authors.lastname: Saïdi
authors.forename: Charlotte
authors.initials: C
authors.lastname: Charpentier
authors.forename: Hicham
authors.initials: H
authors.lastname: Bouhlal
authors.forename: Dominique
authors.initials: D
authors.lastname: Schols
authors.forename: Jan
authors.initials: J
authors.lastname: Balzarini
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Bell
authors.forename: Guido
authors.initials: G
authors.lastname: Vanham
authors.forename: Laurent
authors.initials: L
authors.lastname: Bélec