Conservation and host specificity of Vpr-mediated cell cycle arrest suggest a fundamental role in primate lentivirus evolution and biology

被引:88
作者
Stivahtis, GL
Soares, MA
Vodicka, MA
Hahn, BH
Emerman, M
机构
[1] FRED HUTCHINSON CANC RES CTR, DIV MOL MED, SEATTLE, WA 98104 USA
[2] FRED HUTCHINSON CANC RES CTR, DIV BASIC SCI, SEATTLE, WA 98104 USA
[3] UNIV WASHINGTON, PROGRAM MOL & CELLULAR BIOL, SEATTLE, WA 98195 USA
[4] UNIV ALABAMA, DEPT MED, BIRMINGHAM, AL 35294 USA
[5] UNIV ALABAMA, DEPT MICROBIOL, BIRMINGHAM, AL 35294 USA
关键词
SIMIAN IMMUNODEFICIENCY VIRUS; CROSS-SPECIES TRANSMISSION; AFRICAN-GREEN MONKEYS; TYPE-1; VPR; NUCLEAR-LOCALIZATION; AIDS VIRUSES; SEQUENCE; GENE; INFECTION; PROTEIN;
D O I
10.1128/JVI.71.6.4331-4338.1997
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
The human immunodeficiency virus type 1 (HIV-1) Vpr protein prevents infected cells from passing through mitosis by arresting them in the G(2) phase of the cell cycle. Vpr is conserved among all primate lentiviruses, suggesting an important role in the virus life cycle. Moreover, in this study we show that the ability to cause cell cycle arrest is also conserved in Vpr proteins from a wide variety of both tissue culture-passaged and uncultured human (HIV-1 and HIV-2), sooty mangabey (simian immunodeficiency virus SIVSM), African green monkey (SIVAGM), and Sykes' monkey (SIVSYK) isolates. However, this property is cell type specific and appears to depend on the particular primate species from which the cells are derived. SIVAGM and SIVSYK Vpr proteins are capable of arresting African green monkey cells but are completely inactive in human cells. By contrast, HIV-1, HIV-2, and SIVSM Vpr proteins function in both simian and human cell types, although SIVSM Vpr functions more efficiently in simian cells than it does in human cells. Neither differential protein stability nor subcellular localization explains the species-specific activities of these proteins. These results thus suggest that Vpr exerts its G(2) arrest function by interacting with cellular factors that have evolved differently among the various primate species.
引用
收藏
页码:4331 / 4338
页数:8
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