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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
Author(s) -
Macreadie Ian G.,
Arunagiri Chinniah K.,
Hewish Dean R.,
White Jacinta F.,
Azad A. A.
Publication year - 1996
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1111/j.1365-2958.1996.tb02464.x
Subject(s) - biology , kluyveromyces lactis , schizosaccharomyces pombe , extracellular , candida albicans , intracellular , saccharomyces cerevisiae , programmed cell death , yeast , peptide sequence , amino acid , schizosaccharomyces , microbiology and biotechnology , biochemistry , apoptosis , gene
Summary Vpr is a virion‐associated protein of human immuno‐deficiency virus type 1 (HIV‐1) whose function in acquired immune deficiency syndrome (AIDS) has been uncertain. We previously employed yeast as a model to examine the effects of Vpr on basic cellular functions; intracellular Vpr was shown to cause cell‐growth arrest and structural defects, and these effects were caused by a region of Vpr containing the sequence HFRIGCRHSRIG. Here we show that peptides containing the H(S/F)RIG amino acid sequence motif cause death when added externally to a variety of yeast including Saccharomyces cerevisiae, Kluyveromyces lactis, Candida glabrata, Candida albicans and Schizosaccharomyces pombe . Such peptides rapldly entered the cell from the time of addition, resulting in cell death. Elevated levels of ions, particularly magnesium and calcium ions, abrogated the cytotoxic effect by preventing the Vpr peptides from entering the cells. Extracellular Vpr found in the serum, or breakdown products of extracellular Vpr, may have similar effects to the Vpr peptides described here and could explain the death of uninfected by‐stander cells during AIDS.