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IgG Opsonization of HIV Impedes Provirus Formation in and Infection of Dendritic Cells and Subsequent Long-Term Transfer to T Cells¹

Doris Wilflingseder^2,*, Zoltan Banki^*, Eduardo Garcia, Monika Pruenster, Gerald Pfister, Brigitte Muellauer^*, Damjan S. Nikolic, Christoph Gassner^¶, Christoph G. Ammann^||, Manfred P. Dierich^*, Vincent Piguet and Heribert Stoiber^*

^* Department of Hygiene, Microbiology and Social Medicine, Innsbruck Medical University, Innsbruck, Austria; Department of Dermatology and Venereology, Department of Microbiology and Molecular Medicine, University Hospital and Medical School of Geneva, Geneva, Switzerland; Novartis Institutes for BioMedical Research, Vienna, Austria; Institute for Biomedical Aging Research, Innsbruck, Austria; ^¶ Central Institute for Blood Transfusion and Immunological Department, Innsbruck, Austria; and ^|| Rocky Mountain Laboratories, Laboratory for Persistent Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840

Already at initial phases of infection, HIV is coated with complement fragments. During the chronic phase, when HIV-specific IgGs appear, the virus circulates immune complexed with IgG and complement. Thus, we studied the interaction of dendritic cells (DCs) and DC-T cell cocultures with complement (C)-opsonized and C-IgG-opsonized HIV. HIV infection of monocyte-derived DCs and circulating BDCA-1-positive DCs was significantly reduced upon the presence of virus-specific but non-neutralizing IgGs. DCs exposed to C-Ig-HIV or IgG-opsonized HIV showed an impaired provirus formation and p24 production and a decreased transmission rate to autologous nonstimulated T cells upon migration along a chemokine gradient. This reduced infectivity was also observed in long-term experiments, when T cells were added delayed to DCs exposed to IgG-coated HIV without migration. Similar kinetics were seen when sera from HIV-1-infected individuals before and after seroconversion were used in infection assays. Both C- and C-IgG-opsonized HIV were captured and targeted to a tetraspanin-rich endosome in immature DCs, but differed with respect to MHC class II colocalization. The reduced infection by IgG-opsonized HIV is possibly due to interactions of virus-bound IgG with FcRIIb expressed on DCs. Therefore, the intracellular fate and transmission of immune-complexed HIV seems to differ depending on time and opsonization pattern.

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 the Austrian Science Found (Projects P18960 to D.W. and P14917 to H.S.) and the European Union (Projects TIP-Vac 012116; DEC-Vac 018685), the Ludwig Boltzmann Institute for AIDS Research, and the Federal Government of Tyrol.

² Address correspondence and reprint requests to Dr. Doris Wilflingseder, Department of Hygiene, Microbiology and Social Medicine, Fritz-Pregl-Strasse 3, 6020 Innsbruck, Austria. E-mail address: doris.wilflingseder{at}i-med.ac.at

³ Abbreviations used in this paper: iDC, immature dendritic cell; DC, dendritic cell; CR, complement receptor; VCA, virus capture assay; NHS, normal human serum; o/n, overnight; SN, supernatant.