Human immunodeficiency virus induces phosphorylation of its cell surface receptor

• Published in: Nature (London) Vol. 333; no. 6170; pp. 278 - 280
• Main Authors: Fields, Alan P, Bednarik, Daniel P, Hess, Allan, Stratford May, W
• Format: Journal Article
• Language: English
• Published: London Nature Publishing 19-05-1988; Nature Publishing Group
• Subjects: Acquired immune deficiency syndrome; AIDS; AIDS/HIV; Antigens, Surface - immunology; Biological and medical sciences; Cells, Cultured; Cellular biology; Clone Cells; Fundamental and applied biological sciences. Psychology; HIV - pathogenicity; HIV - physiology; Human immunodeficiency virus; Humans; Lymphocytes; Lymphocytes - immunology; Medical research; Microbiology; Phosphorylation; Proteins; Receptors, HIV; Receptors, Virus - physiology; Replicative cycle, interference, host-virus relations, pathogenicity, miscellaneous strains; Virology; Binding; Phosphorylation; Retroviridae; Virus replication cycle; Molecular interaction; Glycoproteins; Research; Cell subpopulation; Cell surface; Virus; Chemotherapy; Membrane receptor; Infectivity; Antiviral; Human immunodeficiency virus; Virus envelope; Lymphocyte
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/333278a0

AIDS is an immunoregulatory disorder characterized by depletion of the CD4+, helper/inducer lymphocyte population. The causative agent of this disease is the human immunodeficiency virus, HIV, which infects CD4+ cells and leads to cytopathic effects characterized by syncytia formation and cell death. Recent studies have demonstrated that binding of HIV to its cellular receptor CD4 is necessary for viral entry. We find that binding of HIV to CD4 induces rapid and sustained phosphorylation of CD4 which could involve protein kinase C. HIV-induced CD4 phosphorylation can be blocked by antibody against CD4 and monoclonal antibody against the HIV envelope glycoprotein gp120, indicating that a specific interaction between CD4 and gp120 is required for phosphorylation. Electron microscopy shows that a protein kinase C inhibitor does not impair binding of HIV to CD4+ cells, but causes an apparent accumulation of virus particles at the cell surface, at the same time inhibiting viral infectivity. These results indicate a possible role for HIV-induced CD4 phosphorylation in viral entry and identify a potential target for antiviral therapy.