Cytopathic effect of human immunodeficiency virus in T4 cells is linked to the last stage of virus infection.

A principal feature of acquired immunodeficiency syndrome is depletion of T4 lymphocytes, which is partly due to a direct cytopathic effect of the virus. Both syncytial formation (viral-induced cell fusion) and premature cell death have been cited as the major cause for this phenomenon. By kinetic analysis of cell proliferation and cell lysis we show that the cytopathic effect correlates chiefly with virus production from infected cells, including giant syncytial cells. Most T4 cells were, at least transiently, infected by human immunodeficiency virus (human T-lymphotropic virus type IIIB strain); however, after phytohemagglutinin activation, only 10-30% of infected cells express virus (and die) at any one time, indicating that virus production, followed by cell killing, is linked to immune activation and cell differentiation. We also show that an interval exists before viral release, in which expression of viral antigens occurs on the cell surface, suggesting that infected cells are immunogenic before viral production. If so, they may induce a cell-mediated immune response that could minimize dissemination of human immunodeficiency virus, a possibility that has influenced our approaches to the development of a vaccine for prevention of acquired immunodeficiency syndrome.