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Opsonization of HIV with Complement Enhances Infection of Dendritic Cells and Viral Transfer to CD4 T Cells in a CR3 and DC-SIGN-Dependent Manner¹

Hicham Bouhlal^2,*, Nicolas Chomont, Mary Réquena^*, Nadine Nasreddine^*, Héla Saidi^*, Jérôme Legoff^*, Michel D. Kazatchkine, Laurent Bélec^* and Hakim Hocini^*

^* Université René Descartes Paris V and Institut National de la Santé et de la Recherche Médicale, Unité 743, and Equipe d’Immunité et Biothérapie Muqueuse, Institut des Cordeliers, Paris, France; Laboratoire d’Immunologie, Hôpital St. Luc, Centre de Recherches Pavillon Edouard-Asselin, Montréal, Québec, Canada; and Institut National de la Santé et de la Recherche Médicale, Unité 681, Paris, France

In the present study, we demonstrated that opsonization of primary HIV-1 with human complement enhances infection of immature monocyte-derived dendritic cells (iDC) and transmission in trans of HIV to autologous CD4⁺ T lymphocytes. Infection of iDC by opsonized primary R5- and X4-tropic HIV was increased 3- to 5-fold as compared with infection by the corresponding unopsonized HIV. Enhancement of infection was dependent on CR3 as demonstrated by inhibition induced by blocking Abs. The interaction of HIV with CCR5 and CXCR4 on iDC was affected by opsonization. Indeed, stromal-derived factor-1 was more efficient in inhibiting infection of iDC with opsonized R5-tropic HIV-1_BaL (45%) than with heat-inactivated complement opsonized virus and similarly RANTES inhibited more efficiently infection of iDC with opsonized X4-tropic HIV-1_NDK (42%) than with heat-inactivated complement opsonized virus. We also showed that attachment of complement-opsonized virus to DC-specific ICAM-grabbing nonintegrin (DC-SIGN) molecule on iDC and HeLa DC-SIGN⁺ CR3^– cells was 46% and 50% higher compared with heat-inactivated complement opsonized virus, respectively. Hence, Abs to DC-SIGN suppressed up to 80% and 60% the binding of opsonized virus to HeLa cells and iDC, respectively. Furthermore, Abs to DC-SIGN inhibited up to 70% of the infection of iDC and up to 65% of infection in trans of autologous lymphocytes with opsonized virus. These results further demonstrated the role of DC-SIGN in complement opsonized virus uptake and infection. Thus, the virus uses complement to its advantage to facilitate early steps leading to infection following mucosal transmission of HIV.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by Agence National de la Recherches sur le SIDA, Paris, France.

² Address correspondence and reprint requests to Dr. Hicham Bouhlal, Institut National de la Santé et de la Recherche Médicale, Unité 743, Equipe d’Immunité et Biothérapie Muqueuse, Institut des Cordeliers, Escalier E, 2^ème Etage, 15 rue de l’Ecole de Médecine, 75270 Paris Cedex 06, France. E-mail address: hicham.bouhlal{at}u430.bhdc.jussieu.fr

³ Abbreviations used in this paper: DC, dendritic cell; iDC, immature DC; DC-SIGN, DC-specific ICAM-grabbing nonintegrin; AC-OV, activated complement-opsonized virus; HIC-OV, heat-inactivated complement-opsonized virus; SDF, stromal-derived factor; MFI, mean fluorescence intensity.

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