IgG opsonization of HIV impedes provirus formation in and infection of dendritic cells and subsequent long-term transfer to T cells.
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 FcgammaRIIb expressed on DCs. Therefore, the intracellular fate and transmission of immune-complexed HIV seems to differ depending on time and opsonization pattern.
Wilflingseder
Doris
D
Department of Hygiene, Microbiology and Social Medicine, Innsbruck Medical University, Innsbruck, Austria. doris.wilflingseder@i-med.ac.at
Banki
Zoltan
Z
Garcia
Eduardo
E
Pruenster
Monika
M
Pfister
Gerald
G
Muellauer
Brigitte
B
Nikolic
Damjan S
DS
Gassner
Christoph
C
Ammann
Christoph G
CG
Dierich
Manfred P
MP
Piguet
Vincent
V
Stoiber
Heribert
H
D000914:Antibodies, Viral / Q000276:immunology*; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology; D018920:Coculture Techniques; D003165:Complement System Proteins / Q000276:immunology; D003713:Dendritic Cells / Q000821:virology*; D006678:HIV / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology*; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology*; D011533:Proviruses / Q000276:immunology*; D017452:Receptors, IgG / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000821:virology*
D000914:Antibodies, Viral; D015703:Antigens, CD; C080571:Fc gamma receptor IIB; D007140:Immunoglobulin Fab Fragments; D007074:Immunoglobulin G; D017452:Receptors, IgG; D003165:Complement System Proteins