Human immunodeficiency virus type 1 cell cycle control: Vpr is cytostatic and mediates G2 accumulation by a mechanism which differs from DNA damage checkpoint control.
Vpr is a 96-amino-acid protein encoded by human immunodeficiency virus type 1 (HIV-1) that prevents proliferation of infected cells. We have established a system for infection of 100% of a T-cell population with HIV and use this system to show that within the context of HIV-1 infection, Vpr is primarily cytostatic rather than cytotoxic. Vpr acts upstream of dephosphorylation of the mitotic cyclin-dependent kinase, and causes infected cells to accumulate in the G2 stage of the cell cycle. However, some HIV-1 infected cells increase in ploidy and size, accumulating DNA to an 8N level. Furthermore, the mechanism of the Vpr mitotic block is qualitatively different from that of G2 DNA damage checkpoint control.
Bartz
S R
SR
Division of Molecular Medicine, Fred Hutchinson Cancer Research Center, Seattle, Washington 98104, USA.
Rogel
M E
ME
Emerman
M
M
D016203:CDC2 Protein Kinase / Q000378:metabolism; D002453:Cell Cycle; D002460:Cell Line; D016213:Cyclins / Q000378:metabolism; D004249:DNA Damage; D016195:G2 Phase; D016336:Gene Products, vpr / Q000502:physiology*; D015497:HIV-1 / Q000472:pathogenicity / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D011123:Polyploidy; D013601:T-Lymphocytes / Q000166:cytology / Q000821:virology; D054325:vpr Gene Products, Human Immunodeficiency Virus
D016213:Cyclins; D016336:Gene Products, vpr; D054325:vpr Gene Products, Human Immunodeficiency Virus; D016203:CDC2 Protein Kinase