BINDING OF HIV-1 TO ITS RECEPTOR INDUCES TYROSINE PHOSPHORYLATION OF SEVERAL CD4-ASSOCIATED PROTEINS, INCLUDING THE PHOSPHATIDYLINOSITOL 3-KINASE

Cell surface CD4 molecules are known to be important in several physio logical responses of T lymphocytes. The use of human immunodeficiency virus (HIV) particles or purified gp120 molecules as CD4 cross-linking agents has been shown to result in a cascade of intracellular biochem ical events. In addition, we and others have provided evidence suggest ing that virus-mediated CD4 multimerization can lead to modulation of HIV-1 long terminal repeat-dependent activity and virus production. We were thus interested in measuring the effect of HIV-1 particles on in tracellular tyrosine-phosphorylation levels, mostly of CD4-associated proteins. Using the T cell line CEM-T4, we observed that HIV-1 induces an increase in tyrosine phosphorylation of four major proteins physic ally complexed to the CD4 molecule. Immunoblot analysis permitted the identification of two of these proteins, p56(lck) and phosphatidylinos itol 3-kinase (PI 3-kinase) p85 alpha. No concomitant variation in the level of these two CD4-associated proteins was observed after HIV-l-i nduced CD4 cross-linking. To our knowledge, this is the first report l inking HIV-l-mediated CD4 multimerization to an increase in tyrosine p hosphorylation of the PI 3-kinase complex. The four CD4-associated mol ecules described in this report are most likely implicated in virus-in duced CD4-linked signaling events. (C) 1997 Academic Press.