EXTRACELLULAR ADDITION OF A DOMAIN OF HIV-1 VPR CONTAINING THE AMINO-ACID-SEQUENCE MOTIF H(S F)RIG CAUSES CELL-MEMBRANE PERMEABILIZATION AND DEATH/

Vpr is a virion-associated protein of human immunodeficiency virus typ e 1 (HIV-1) whose function in acquired immune deficiency syndrome (AID S) has been uncertain. We previously employed yeast as a model to exam ine the effects of Vpr on basic cellular functions; intracellular Vpr was shown to cause cell-growth arrest and structural defects, and thes e effects were caused by a region of Vpr containing the sequence HFRIG CRHSRIG. Here we show that peptides containing the H(S/F)RIG amino aci d sequence motif cause death when added externally to a variety of yea st including Saccharomyces cerevisiae, Kluyveromyces lactis, Candida g labrata, Candida albicans and Schizosaccharomyces pombe. Such peptides rapidly entered the cell from the time of addition, resulting in cell death. Elevated levels of ions, particularly magnesium and calcium io ns, abrogated the cytotoxic effect by preventing the Vpr peptides from entering the cells. Extracellular Vpr found in the serum, or breakdow n products of extracellular Vpr, may have similar effects to the Vpr p eptides described here and could explain the death of uninfected bysta nder cells during AIDS.