Evidence for the role of CR1 (CD35), in addition to CR2 (CD21), in facilitating infection of human T cells with opsonized HIV.
Complement activation by HIV results in the binding of C3 fragments to the gp160 complex and enhanced infection of C3 receptor-bearing target cells. We have studied complement-mediated enhancement of infection of the human CD4-positive T-cell line HPB-ALL which expresses the CR1 (CD35) and CR2 (CD21) receptors for C3. CR1 and CR2 are present on 15% and 40% of normal peripheral blood CD4-positive T lymphocytes respectively. Opsonization of the virus with complement resulted in a 3- to 10-fold enhancement of infection of HPB-ALL cells, as assessed by measuring the release of p24 antigen in culture supernatants throughout the culture period. Blockade of CR2 with cross-linked anti-CR2 monoclonal antibodies decreased infection to the level observed with unopsonized virus. Blocking CR1 reduced complement-mediated infection by 50-80%. Experiments using serum deficient in complement factor I demonstrated that CR1 mediates the interaction between opsonized virus and T cells in addition to its ability to serve as a cofactor for the cleavage of C3b into smaller fragments that interact with CR2. A requirement for CD4 in complement-mediated enhancement of infection was observed with HIV-1 Bru but not with HIV-1 RF. Thus, CR1 and CR2 contribute in an independent and complementary fashion to penetration of opsonized virus into complement receptor-expressing T cells. Involvement of CD4 in infection with opsonized virus depends on the viral strain.
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INSERM U 28, Hôpital Broussais, Paris, France.
Kazatchkine
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MD
Fischer
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D015704:CD4 Antigens / Q000502:physiology; D003165:Complement System Proteins / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology / Q000502:physiology*; D006801:Humans; D009895:Opsonin Proteins; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000382:microbiology; D017463:Receptors, Complement 3b / Q000502:physiology*; D017464:Receptors, Complement 3d / Q000502:physiology*; D013601:T-Lymphocytes / Q000382:microbiology*; D014407:Tumor Cells, Cultured
D015704:CD4 Antigens; D009895:Opsonin Proteins; D017463:Receptors, Complement 3b; D017464:Receptors, Complement 3d; D003165:Complement System Proteins