Ligation of CR1 (C3b receptor, CD35) on CD4+ T lymphocytes enhances viral replication in HIV-infected cells.
The present study provides evidence for a role of the C3b receptor, CR1 (CD35), in activation of HIV replication in CD4+ T lymphocytes. Ligation of CR1 with cross-linked anti-receptor MoAbs or with aggregated C3b enhanced transcription of viral genes and the release of p24 and RT activity from cultures of purified normal CD4+ T lymphocytes that had been infected with HIV-1 in vitro. No effect was observed upon ligation of CR2 (CD21), a C3 receptor that is also expressed on human CD4+ T cells. Cross-linking of CR1 also enhanced HIV replication in peripheral blood CD4+ lymphocytes isolated from HIV+ individuals. The enhancing effect of CR1 was not related to a mitogenic effect induced by stimulation of the receptor on T cells. The CR1 specificity of the enhancing effect was established by the observation that the addition of soluble recombinant CR1 to the cultures abolished the enhancement of p24 release induced by anti-CR1 MoAbs. Our results suggest that HIV replication may be triggered in resting HIV-infected CD4+ T lymphocytes through interaction with C3b-bearing immune complexes or particles.
Mouhoub
A
A
INSERM U430, Hôpital Broussais, Paris, France.
Delibrias
C C
CC
Fischer
E
E
Boyer
V
V
Kazatchkine
M D
MD
D000911:Antibodies, Monoclonal; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism / Q000821:virology*; D002455:Cell Division; D002460:Cell Line; D002478:Cells, Cultured; D016655:HIV Core Protein p24 / Q000096:biosynthesis; D006679:HIV Seropositivity / Q000503:physiopathology; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D008024:Ligands; D012333:RNA, Messenger / Q000096:biosynthesis; D017463:Receptors, Complement 3b / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics; D014775:Virus Activation; D014779:Virus Replication / Q000502:physiology*
D000911:Antibodies, Monoclonal; D016655:HIV Core Protein p24; D008024:Ligands; D012333:RNA, Messenger; D017463:Receptors, Complement 3b; D014409:Tumor Necrosis Factor-alpha