TY - JOUR
T1 - Human immunodeficiency virus type 1 viral protein R (Vpr) arrests cells in the G2 phase of the cell cycle by inhibiting p34(cdc2) activity
AU - He, J.
AU - Choe, S.
AU - Walker, R.
AU - Di Marzio, P.
AU - Morgan, D. O.
AU - Landau, N. R.
PY - 1995
Y1 - 1995
N2 - 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 G2/M phase of the cell cycle. In cycling cells, progression from G2 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(cdc2) (Thr-14 and Tyr- 15). We show here that Vpr arrests the cell cycle in G2 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 G2 arrest. These findings strongly suggest that Vpr arrests cells in G2 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.
AB - 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 G2/M phase of the cell cycle. In cycling cells, progression from G2 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(cdc2) (Thr-14 and Tyr- 15). We show here that Vpr arrests the cell cycle in G2 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 G2 arrest. These findings strongly suggest that Vpr arrests cells in G2 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.
UR - http://www.scopus.com/inward/record.url?scp=0028853961&partnerID=8YFLogxK
U2 - 10.1128/jvi.69.11.6705-6711.1995
DO - 10.1128/jvi.69.11.6705-6711.1995
M3 - Article
C2 - 7474080
AN - SCOPUS:0028853961
SN - 0022-538X
VL - 69
SP - 6705
EP - 6711
JO - Journal of Virology
JF - Journal of Virology
IS - 11
ER -