Complement dependent trapping of infectious HIV in human lymphoid tissues.
OBJECTIVE
HIV-1 bound extracellularly to follicular dendritic cells (FDC) in germinal centers (GC) of lymphoid tissues (LT) represents the largest viral reservoir in HIV-infected individuals; however there is no direct evidence as to whether HIV trapped in human GC remains infectious. In the GC, complement receptors and Fc gamma receptors have been suggested to participate in trapping of HIV; therefore, the relative contribution of complement- and Fc gamma receptors in binding HIV on LT was investigated and the infectivity of this virus was tested.


METHODS
As it is difficult to isolate FDC without contaminations of productively infected cells, HIV was detached from LT of HIV positive individuals using antibodies blocking complement- and Fc gamma receptors. Isolated virus was tested in an infectivity assay.


METHODS
HIV detached from LT was quantified by HIV p24 ELISA, PCR and in an in vitro infectivity assay. Presence and accessibility of viral envelope proteins, complement factors and immunoglobulins on the surface of detached viral particles were evaluated through viral capture by respective antibodies.


RESULTS
Although both C3d-fragments and IgG molecules were identified on the surface of HIV detached from LT, trapping of HIV was mediated solely by CR2-C3d interactions, whereas contribution of Fc gamma receptors was not detectable. Infectivity assays with HIV stripped from LT of HIV positive individuals revealed that in four out of ten patients HIV particles were infectious.


CONCLUSIONS
These findings indicate that in the GC infectious virus is trapped on CR2-expressing FDC (or B cells). Reduction of this pool of HIV could be a therapeutic goal.
Bánki
Zoltán
Z
Department of Hygiene, Microbiology and Social Medicine, Innsbruck Medical University and Ludwig-Boltzmann-Institute for AIDS Research, 6020 Innsbruck, Austria.
Kacani
Laco
L
Rusert
Peter
P
Pruenster
Monika
M
Wilflingseder
Doris
D
Falkensammer
Barbara
B
Stellbrink
Hans-Jürgen
HJ
van Lunzen
Jan
J
Trkola
Alexandra
A
Dierich
Manfred P
MP
Stoiber
Heribert
H
D002478:Cells, Cultured; D015658:HIV Infections / Q000276:immunology / Q000821:virology*; D015497:HIV-1 / Q000276:immunology / Q000302:isolation & purification* / Q000472:pathogenicity; D006801:Humans; D007074:Immunoglobulin G / Q000032:analysis; D008221:Lymphoid Tissue / Q000276:immunology / Q000821:virology*; D014066:Palatine Tonsil / Q000276:immunology / Q000821:virology; D011446:Prospective Studies; D017464:Receptors, Complement 3d / Q000276:immunology*; D017452:Receptors, IgG / Q000276:immunology; D014764:Viral Proteins / Q000032:analysis
D007074:Immunoglobulin G; D017464:Receptors, Complement 3d; D017452:Receptors, IgG; D014764:Viral Proteins