Infection of monocytes by human immunodeficiency virus type 1 blocked by inhibitors of CD4-gp120 binding, even in the presence of enhancing antibodies.
Infection of monocyte/macrophages (M/M) by a variety of viruses (including HIV-1) has been shown to be enhanced in the presence of low concentrations of antiviral antibodies. This process has been hypothesized as occurring through binding of the virus-antibody complex to Fc or complement receptors followed by endocytosis. In the current study, we explored whether such a mechanism might provide a CD4-independent route of infection by HIV-1 for any of several populations of M/M. In the absence of anti-HIV antibodies, replication of HIV-1 in M/M was blocked by viral binding inhibitors such as soluble CD4 or OKT4A mAb. Furthermore, while infection of the M/M populations by a low multiplicity of infection of HIV-1 was found to be somewhat enhanced by the presence of very low concentrations of anti-HIV antibodies, this process was also consistently inhibited by recombinant soluble CD4 and by OKT4A antibody. These results suggest that under the variety of conditions studied, CD4 binding was an essential step in the infection of M/M by HIV. Moreover, they are consistent with the notion that "enhancing" antibodies may serve to concentrate HIV onto CD4 receptors or, alternately, may act at other steps in the process of viral entry and replication.
Perno
C F
CF
Clinical Oncology Program, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892.
Baseler
M W
MW
Broder
S
S
Yarchoan
R
R
D000911:Antibodies, Monoclonal / Q000276:immunology; D015703:Antigens, CD / Q000276:immunology; D000954:Antigens, Surface / Q000032:analysis; D015704:CD4 Antigens / Q000276:immunology*; D002460:Cell Line; D002478:Cells, Cultured; D004261:DNA Replication; D015483:HIV Antibodies / Q000276:immunology*; D015699:HIV Envelope Protein gp120 / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology / Q000502:physiology*; D006684:HLA-DR Antigens / Q000032:analysis; D006801:Humans; D007700:Kinetics; D009000:Monocytes / Q000276:immunology / Q000382:microbiology* / Q000502:physiology; D010587:Phagocytosis
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000954:Antigens, Surface; D015704:CD4 Antigens; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D006684:HLA-DR Antigens