A C-TERMINAL DOMAIN OF HIV-1-ACCESSORY PROTEIN VPR IS INVOLVED IN PENETRATION, MITOCHONDRIAL DYSFUNCTION AND APOPTOSIS OF HUMAN CD4(+) LYMPHOCYTES

We have previously shown that expression of HIV-1 vpr in yeast results in cell growth arrest and structural defects, and identified a C-term inal domain of Vpr as being responsible for these effects in yeast.(1) In this report we show that recombinant Vpr and C-terminal peptides o f Vpr containing the conserved sequence HFRIGCRHSRIG caused permeabili zation of CD4(+) T lymphocytes, a dramatic reduction of mitochondrial membrane potential and finally cell death, Vpr and Vpr peptides contai ning the conserved sequence rapidly penetrated cells, co-localized wit h the DNA, and caused increased granularity and formation of dense apo ptotic bodies, The above results suggest that Vpr treated cells underg o apoptosis and this was confirmed by demonstration of DNA fragmentati on by the highly sensitive TUNEL assay, Our results, together with the demonstration of extracellular Vpr in HIV infected individuals,(2,3) suggest the possibility that extracellular Vpr could contribute to the apoptotic death and depletion of bystander cells in lymphoid tissues( 4,5) during HIV infection.