Macreadie I G, Arunagiri C K, Hewish D R, White J F, Azad A A
Biomolecular Research Institute, Division of Biomolecular Engineering, Parkville, Victoria, Australia.
Mol Microbiol. 1996 Mar;19(6):1185-92. doi: 10.1111/j.1365-2958.1996.tb02464.x.
Vpr is a virion-associated protein of human immunodeficiency 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 rapidly 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 bystander cells during AIDS.
Vpr是1型人类免疫缺陷病毒（HIV-1）的一种病毒体相关蛋白，其在获得性免疫缺陷综合征（AIDS）中的功能尚不确定。我们之前以酵母为模型来研究Vpr对基本细胞功能的影响；结果显示细胞内的Vpr会导致细胞生长停滞和结构缺陷，且这些影响是由Vpr中包含HFRIGCRHSRIG序列的区域引起的。在此我们表明，含有H(S/F)RIG氨基酸序列基序的肽在添加到包括酿酒酵母、乳酸克鲁维酵母、光滑念珠菌、白色念珠菌和粟酒裂殖酵母在内的多种酵母外部时会导致细胞死亡。此类肽从添加之时起便迅速进入细胞，从而导致细胞死亡。离子水平升高，尤其是镁离子和钙离子，可通过阻止Vpr肽进入细胞来消除细胞毒性作用。血清中发现的细胞外Vpr或细胞外Vpr的分解产物可能具有与此处所述Vpr肽类似的作用，并可解释AIDS期间未感染的旁观者细胞的死亡。
