CR1 (CD35) and CR3 (CD11b/CD18) mediate infection of human monocytes and monocytic cell lines with complement-opsonized HIV independently of CD4.
Peripheral blood and tissue mononuclear phagocytes serve as major viral reservoirs in HIV-infected individuals. We investigated the role of complement receptors CR1 (CD35) and CR3 (CD11b/CD18) in mediating productive infection with complement-opsonized HIV-1 and HIV-2 of cultured normal human peripheral blood monocytes, the promonocytic cell line THP-1, the monocytic cell line Mono Mac 6 and the glial cell line U251-MG. Cells were infected with the HTLV-IIIB strain of HIV-1 or the LAV-2 strain of HIV-2 that had been preopsonized with fresh human normal HIV seronegative serum. Productive infection was assessed by syncytia formation, the MTT cytotoxicity assay and/or release of p24 antigen in culture supernatants. Using suboptimal amounts of virus to infect the cells, we observed a higher and earlier productive infection of the cells with complement-opsonized HIV than with unopsonized virus. The enhancing effect of complement was totally suppressed by blocking CR1 or CR3 function with F(ab)'2 fragments of anti-receptor MoAbs; while blocking of the LFA-1 antigen had no effect. The infection of monocytic cells with complement-opsonized virus occurred independently of CD4 since it was not inhibited by F(ab)'2 fragments of a MoAb against the gp120 binding site of CD4 and since infection also occurred with Mono Mac 6 and U251-MG cells, which lack expression of the CD4 antigen and of CD4 mRNA. These observations suggest that complement may mediate productive infection of cells of the monocytic lineage with 'lymphocytotropic' HIV strains independently of CD4.
Thieblemont
N
N
INSERM U 28, Hôpital Broussais, Paris, France.
Haeffner-Cavaillon
N
N
Ledur
A
A
L'Age-Stehr
J
J
Ziegler-Heitbrock
H W
HW
Kazatchkine
M D
MD
D015703:Antigens, CD / Q000096:biosynthesis; D015152:Blotting, Northern; D015704:CD4 Antigens / Q000235:genetics / Q000276:immunology; D002460:Cell Line; D002478:Cells, Cultured; D002999:Clone Cells; D003165:Complement System Proteins / Q000276:immunology*; D005434:Flow Cytometry; D006678:HIV / Q000276:immunology* / Q000502:physiology; D006801:Humans; D016130:Immunophenotyping; D016177:Macrophage-1 Antigen / Q000276:immunology*; D009000:Monocytes / Q000382:microbiology*; D009895:Opsonin Proteins / Q000276:immunology; D012313:RNA / Q000032:analysis; D017463:Receptors, Complement 3b / Q000276:immunology*
D015703:Antigens, CD; D015704:CD4 Antigens; D016177:Macrophage-1 Antigen; D009895:Opsonin Proteins; D017463:Receptors, Complement 3b; D012313:RNA; D003165:Complement System Proteins