Involvement of a leukocyte adhesion receptor (LFA-1) in HIV-induced syncytium formation.
Cell fusion (syncytium formation) is a major cytopathic effect of infection by human immunodeficiency virus (HIV) and may also represent an important mechanism of CD4+ T-cell depletion in individuals infected with HIV. Syncytium formation requires the interaction of CD4 on the surface of uninfected cells with HIV envelope glycoprotein gp120 expressed on HIV-infected cells. However, several observations suggest that molecules other than CD4 play a role in HIV-induced cell fusion. The leukocyte adhesion receptor LFA-1 is involved in a broad range of leukocyte interactions mediated by diverse receptor-ligand systems including CD4-class II major histocompatibility complex (MHC) molecules. Possible mimicry of class II MHC molecules by gp120 in its interaction with CD4 prompted an examination of the role of LFA-1 in HIV-induced cell fusion. A monoclonal antibody against LFA-1 completely inhibited HIV-induced syncytium formation. The antibody did not block binding of gp120 to CD4. This demonstrates that a molecule other than CD4 is also involved in cell fusion mediated by HIV.
Hildreth
J E
JE
Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
Orentas
R J
RJ
D000911:Antibodies, Monoclonal; D000943:Antigens, Differentiation / Q000276:immunology / Q000502:physiology*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology; D002459:Cell Fusion; D002460:Cell Line; D003588:Cytopathogenic Effect, Viral; D006678:HIV / Q000276:immunology / Q000502:physiology*; D015699:HIV Envelope Protein gp120; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006801:Humans; D016169:Lymphocyte Function-Associated Antigen-1; D010835:Phytohemagglutinins / Q000494:pharmacology; D012191:Retroviridae Proteins / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology / Q000382:microbiology*; D014759:Viral Envelope Proteins / Q000276:immunology
D000911:Antibodies, Monoclonal; D000943:Antigens, Differentiation; D000945:Antigens, Differentiation, T-Lymphocyte; D015699:HIV Envelope Protein gp120; D000949:Histocompatibility Antigens Class II; D016169:Lymphocyte Function-Associated Antigen-1; D010835:Phytohemagglutinins; D012191:Retroviridae Proteins; D014759:Viral Envelope Proteins