HIV-induced apoptosis requires the CD4 receptor cytoplasmic tail and is accelerated by interaction of CD4 with p56(lck)

The roles of the CD4 receptor and the src kinase p56(lck) were examined in the process of HIV-induced apoptosis of CD4(+) T lymphocytes. The presence of the CD4 cytoplasmic tail was found to be essential in delivering an apoptotic signal, and interaction of CD4 with p56(lck) potentiated HIV-induced apoptosis. Apoptosis, but not HIV replication, was abrogated by deleting the NH2-terminal intracytoplasmic tail of CD4, or by mutating the two critical cysteines in this tail that are responsible for CD4-p56(lck) interaction. Introduction of p56(lck) in C8166-45 or MT-2 cells, CD4(+) T cell lines deficient for this protein, greatly increased HIV-induced apoptosis and syncytium formation. The ability of p56(lck) to deliver an apoptotic signal did not depend on its kinase function, since a kinase-deficient mutant was as effective as its normal counterpart in inducing apoptosis, suggesting that p56(kk) may act as an adapter to anchor other proteins to transduce the death signal.