Human immunodeficiency virus type 1 viral protein R (Vpr) arrests cells in the G2 phase of the cell cycle by inhibiting p34(cdc2) activity

J. He, S. Choe, R. Walker, P. Di Marzio, D. O. Morgan, N. R. Landau

Research output: Contribution to journalArticle

748 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)6705-6711
Number of pages7
JournalJournal of virology
Volume69
Issue number11
DOIs
StatePublished - 1995

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