Dual role of the HIV-1 vpr protein in the modulation of the apoptotic response of T cells

We investigated the effect of vpr, physiologically expressed during the cou rse of an acute HIV-1 infection, on the response of infected cells to apopt otic stimuli as well as on the HIV-induced apoptosis, At 48 h after infecti on, Jurkat cells exhibited a lower susceptibility to undergo apoptosis with respect to uninfected cells. This effect was not observed following infect ion with either a vpr-mutated virus or a wild-type strain in the presence o f antisense oligodeoxynucleotides targeted at vpr mRNA, Single-cell analysi s, aimed at simultaneously identifying apoptotic and infected cells, reveal ed that resistance to apoptosis correlated with productive infection. Notab ly, vpr-dependent protection from induced apoptosis was also observed in HI V-l-infected PBMC, In contrast, at later stages of infection, a marked incr ease in the number of cells spontaneously undergoing apoptosis was detected in infected cultures. This virus-induced apoptosis involved vpr expression and predominantly occurred in productively infected cells. These results i ndicate that HIV-1 vpr can exert opposite roles in the regulation of apopto sis, which may depend on the level of its intracellular expression at diffe rent stages of HIV-I infection. The dual function of vpr represents a novel mechanism in the complex strategy evolved by HIV to influence the turnover of T lymphocytes leading to either viral persistence or virus release and spreading.