Detachment of human immunodeficiency virus type 1 from germinal centers by blocking complement receptor type 2.
After the transition from the acute to the chronic phase of human immunodeficiency virus (HIV) infection, complement mediates long-term storage of virions in germinal centers (GC) of lymphoid tissue. The contribution of particular complement receptors (CRs) to virus trapping in GC was studied on tonsillar specimens from HIV-infected individuals. CR2 (CD21) was identified as the main binding site for HIV in GC. Monoclonal antibodies (MAb) blocking the CR2-C3d interaction were shown to detach 62 to 77% of HIV type 1 from tonsillar cells of an individual in the presymptomatic stage. Although they did so at a lower efficiency, these antibodies were able to remove HIV from tonsillar cells of patients under highly active antiretroviral therapy, suggesting that the C3d-CR2 interaction remains a primary entrapment mechanism in treated patients as well. In contrast, removal of HIV was not observed with MAb blocking CR1 or CR3. Thus, targeting CR2 may facilitate new approaches toward a reduction of residual virus in GC.
Institute for Hygiene and Social Medicine, University of Innsbruck, A-6020 Innsbruck, Austria.
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L
Kacani
W M
WM
Prodinger
G M
GM
Sprinzl
M G
MG
Schwendinger
M
M
Spruth
H
H
Stoiber
S
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Döpper
S
S
Steinhuber
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F
Steindl
M P
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Dierich
D000328:Adult; D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D001667:Binding, Competitive; D015933:Complement C3d / Q000276:immunology / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D018858:Germinal Center / Q000276:immunology / Q000821:virology*; D015497:HIV-1 / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D014066:Palatine Tonsil / Q000276:immunology / Q000821:virology*; D012367:RNA, Viral / Q000032:analysis; D017464:Receptors, Complement 3d / Q000276:immunology / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D012367:RNA, Viral; D017464:Receptors, Complement 3d; D015933:Complement C3d