Factor I-mediated processing of complement fragments on HIV immune complexes targets HIV to CR2-expressing B cells and facilitates B cell-mediated transmission of opsonized HIV to T cells.
Our study demonstrates that binding of complement-opsonized HIV to complement receptor type 1 on human erythrocytes (E) via C3b fragments is followed by a rapid normal human serum-mediated detachment of HIV from E. The release was dependent on the presence of factor I indicating a conversion of C3b fragments to iC3b and C3d on the viral surface. This in turn resulted in an efficient binding of opsonized HIV to CR2-expressing B cells, thus facilitating B cell-mediated transmission of HIV to T cells. These data provide a new dynamic view of complement opsonization of HIV, suggesting that association of virus with E might be a transient phenomenon and the factor I-mediated processing of C3b to iC3b and C3d on HIV targets the virus to complement receptor type 2-expressing cells. Thus, factor I in concert with CR1 on E and factor H in serum due to their cofactor activity are likely to be important contributors for the generation of C3d-opsonized infectious HIV reservoirs on follicular dendritic cells and/or B cells in HIV-infected individuals.
Bánki
Zoltán
Z
Department of Hygiene, Microbiology and Social Medicine, Innsbruck Medical University, Austria. Zolta.Banki@uibk.ac.at
Wilflingseder
Doris
D
Ammann
Christoph G
CG
Pruenster
Monika
M
Müllauer
Brigitte
B
Holländer
Karoline
K
Meyer
Martina
M
Sprinzl
Georg M
GM
van Lunzen
Jan
J
Stellbrink
Hans-Jürgen
HJ
Dierich
Manfred P
MP
Stoiber
Heribert
H
D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000821:virology*; D003165:Complement System Proteins / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D005340:Fibrinogen / Q000378:metabolism*; D006678:HIV / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology* / Q000821:virology; D006801:Humans; D007700:Kinetics; D017464:Receptors, Complement 3d / Q000276:immunology*; D044967:Serum; D013601:T-Lymphocytes / Q000276:immunology / Q000821:virology*
D017464:Receptors, Complement 3d; D005340:Fibrinogen; D003165:Complement System Proteins