Vpu increases susceptibility of human immunodeficiency virus type 1 infected cells to Fas killing

The importance of the Fas death pathway in human immunodeficiency virus (HI V) infection has been the subject of many studies. Missing from these studi es is direct measurement of infected cell susceptibility to Fas-induced dea th. To address this question, we investigated whether T cells infected with HIV are more susceptible to Fas-induced death. We found that Fas cross-lin king caused a decrease in the number of HIV-infected Jurkat T cells and CD4 (+) peripheral blood leukocytes (PBLs). We confirmed this finding by demons trating that there were more apoptotic infected than uninfected cells after Fas ligation, The increase in sensitivity of HIV-infected cells to Fas kil ling mapped to vpu, while nef, vif, vpr, and second exon of tat did not app ear to contribute. Furthermore, expression of Vpu in Jurkat T cells rendere d them more susceptible to Fas-induced death. These results show that HIV-i nfected cells are more sensitive to Fas-induced death and that the Vpu prot ein of HIV contributes to this sensitivity. The increased sensitivity of HI V-infected cells to Fas-induced death might help explain why these cells ha ve such a short in vivo half-life.