Complement mediates human immunodeficiency virus type 1 infection of a human T cell line in a CD4- and antibody-independent fashion.
Incubation of the human T cell lymphotropic virus (HTLV)-IIIB and HTLV-RF strains of human immunodeficiency virus type 1 (HIV-1) with normal seronegative human serum under conditions that allow complement activation resulted in enhancement of infection of the MT2 human T cell line cultured in the presence of low amounts of virus. Infection of MT2 cells was assessed by measuring reverse transcriptase activity in supernatants at day 9 of culture. Complement activation by viral suspensions occurred through the alternative pathway. Opsonization of HTLV-RF viral particles with complement was sufficient to allow a productive infection to occur in cells exposed to suboptimal amounts of virus. Infection of MT2 cells with suboptimal amounts of serum-opsonized HIV-1 was suppressed by blocking the C3dg receptor (CR2, CD21) on MT2 cells with monoclonal anti-CR2 antibody and rabbit F(ab')2 anti-mouse immunoglobulin antibodies. Blocking of the gp120-binding site on CD4 under similar experimental conditions had no inhibitory effect on infection of MT2 cells with opsonized virus. Opsonization of HIV-1 with seronegative serum also resulted in a CR2-mediated enhancement of the infection of normal peripheral blood mononuclear cells and T lymphocytes. These results indicate that complement in the absence of antibody may enhance infection of C3 receptor-bearing T cells with HIV-1, and that the interaction of opsonized virus with the CR2 receptor may result by itself in the infection of target T cells in a CD4- and antibody-independent fashion.
Boyer
V
V
Unité de Recherche sur les Hépatites, le SIDA, et les Rétrovirus Humains, INSERM U 271, Lyon, France.
Desgranges
C
C
Trabaud
M A
MA
Fischer
E
E
Kazatchkine
M D
MD
D000163:Acquired Immunodeficiency Syndrome / Q000473:pathology / Q000503:physiopathology*; D000944:Antigens, Differentiation, B-Lymphocyte / Q000276:immunology / Q000378:metabolism / Q000502:physiology; D015704:CD4 Antigens / Q000276:immunology / Q000502:physiology*; D002460:Cell Line; D003165:Complement System Proteins / Q000378:metabolism / Q000502:physiology*; D015483:HIV Antibodies / Q000276:immunology / Q000502:physiology*; D015497:HIV-1 / Q000276:immunology / Q000302:isolation & purification*; D006801:Humans; D009000:Monocytes / Q000276:immunology / Q000382:microbiology / Q000648:ultrastructure; D011951:Receptors, Complement / Q000276:immunology / Q000378:metabolism / Q000502:physiology; D017464:Receptors, Complement 3d; D013601:T-Lymphocytes / Q000276:immunology / Q000382:microbiology* / Q000648:ultrastructure
D000944:Antigens, Differentiation, B-Lymphocyte; D015704:CD4 Antigens; D015483:HIV Antibodies; D011951:Receptors, Complement; D017464:Receptors, Complement 3d; D003165:Complement System Proteins