Mapping of HIV-1 determinants of apoptosis in infected T cells

HIV-1 infection leads to death of CD4(+) T cells in vivo and in vitro, alth ough the mechanisms of this cell death are not well defined. We used flow c ytometry to concurrently analyze infection and apoptosis of the CD4(+) CEM T cell line and human peripheral blood mononuclear cells (PBMC). Surprising ly, T cells productively infected with HIV-1 IIIB showed less apoptosis tha n control, uninfected T cells. This relative paucity of apoptosis was a cha racteristic of IIIB, since a large number of cells infected with the viral clone, HIV-1 NL4-3, were apoptotic The nef, vpr, and vpu gene products were not responsible for apoptosis of NL4-3-infected cells, since NL4-3 Delta V pr Delta Vpu Delta Nef and HXB-2 (a nef, vpr, and vpu triple mutant derived from IIIB) also killed infected cells. Moreover, only IIIB-infected cells showed a resistance to background levels of apoptosis. Thus, the apoptotic (and antiapoptotic) properties of HIV-1 do not map solely to mutations in n ef, vpr, or vpu. We postulate that, in vivo, HIV variants that do not induc e rapid apoptosis in the cells they infect may have a selective advantage. (C) 1998 Academic Press.