HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 VIRAL-PROTEIN-R (VPR) ARRESTS CELLS IN THE G(2) PHASE OF THE CELL-CYCLE BY INHIBITING P34(CDC2) ACTIVITY

被引:783
作者
HE, JL
CHOE, S
WALKER, R
DIMARZIO, P
MORGAN, DO
LANDAU, NR
机构
[1] NYU,SCH MED,AARON DIAMOND AIDS RES CTR,NEW YORK,NY 10016
[2] NYU,SCH MED,DEPT PATHOL,NEW YORK,NY 10016
[3] UNIV CALIF SAN FRANCISCO,DEPT PHYSIOL,SAN FRANCISCO,CA 94143
关键词
D O I
10.1128/JVI.69.11.6705-6711.1995
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
The Vpr accessory gene product of human immunodeficiency virus types 1 and 2 and simian immunodeficiency virus is believed to play a role in permitting entry of the viral core into the nucleus of nondividing cells. A second role for Vpr was recently suggested by Rogel et al, (M. E. Rogel, L. I. Wu, and M. Emerman, J. Virol, 69:882-888, 1995), who showed that Vpr prevents the establishment in vitro of chronically infected HIV producer cell lines, apparently by causing infected cells to arrest in the G(2)/M phase of the cell cycle. In cycling cells, progression from G(2) to M phase is driven by activation of the p34(cdc2)/cyclin B complex, an event caused; in part, by dephosphorylation of two regulatory amino acids of p34(cdc)2 (Thr-14 and Tyr-15). We show here that Vpr arrests the cell cycle in G(2) by preventing the activation of the p34(cdc2)/cyclin B complex. Vpr expression in cells caused p34(cdc2) to remain in the phosphorylated, inactive state, p34(cdc2)/cyclin B complexes immunoprecipitated from cells expressing Vpr were almost completely inactive in a histone H1 kinase assay. Coexpression of a constitutively active mutant p34(cdc2) molecule with Vpr relieved the G(2) arrest. These findings strongly suggest that Vpr arrests cells in G(2) by preventing the activation of the p34(cdc2)/cyclin B complex that is required for entry into M phase. In vivo, Vpr might, by preventing p34(cdc2) activation, delay or prevent apoptosis of infected cells. This would increase the amount of virus each infected cell produced.
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页码:6705 / 6711
页数:7
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