Mechanism(s) promoting HIV-1 infection of primary unstimulated T lymphocytes in autologous B cell/T cell co-cultures.
Resting CD4(+) T cells in the lymphoid tissue (LT) are essential producers of virions at the beginning of HIV infection in vivo. We previously developed a model that allowed in vitro infection of non-prestimulated T lymphocytes in the presence of autologous B lymphocytes and complement. In this study, we try to clarify the mechanism(s) responsible for virus transmission in unstimulated autologous B cell/T cell co-cultures. Ex vivo analyses of patient plasma samples revealed that HIV was opsonized. Flow cytometry showed that opsonized virus preferentially bound to complement receptor (CR)-2 on B lymphocytes in primary B cell/T cell co-cultures. As indicated by cytokine measurements and transwell experiments, soluble factors seemed to play a minor role in enabling infection. Rather, direct interaction between B and T lymphocytes and direct binding of opsonized virus to CR2 on B cells turned out to be essential for productive infection. Antibodies blocking cell-cell adhesion inhibited p24 antigen production. An anti-CR2 antibody blocking C3d-CR2 binding also significantly reduced viral replication. Since the infection of unstimulated T cells by opsonized primary HIV isolates in the presence of B cells was highly efficient independent of the tropism of the virus, this mechanism may be critical in the pathogenesis of HIV.
Döpper
Susanne
S
Institute of Hygiene and Social Medicine, Ludwig Boltzmann Insitute for AIDS Research, University Innsbruck, Austria.
Wilflingseder
Doris
D
Prodinger
Wolfgang M
WM
Stiegler
Gabriele
G
Speth
Cornelia
C
Dierich
Manfred P
MP
Stoiber
Heribert
H
D000906:Antibodies / Q000494:pharmacology; D015703:Antigens, CD / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology* / Q000821:virology; D018122:B7-1 Antigen / Q000378:metabolism; D051940:B7-2 Antigen; D040881:CD11a Antigen / Q000378:metabolism; D018106:CD28 Antigens / Q000378:metabolism; D002453:Cell Cycle; D002478:Cells, Cultured; D018920:Coculture Techniques; D003176:Complement C3 / Q000378:metabolism; D015658:HIV Infections / Q000209:etiology* / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000276:immunology / Q000302:isolation & purification / Q000472:pathogenicity*; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism; D017464:Receptors, Complement 3d / Q000037:antagonists & inhibitors; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000821:virology*; D014779:Virus Replication
D000906:Antibodies; D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D040881:CD11a Antigen; D018106:CD28 Antigens; C497964:CD86 protein, human; D003176:Complement C3; D007074:Immunoglobulin G; D008562:Membrane Glycoproteins; D017464:Receptors, Complement 3d; D018799:Intercellular Adhesion Molecule-1