Human immunodeficiency virus type 1 Vpr arrests the cell cycle in G2 by inhibiting the activation of p34cdc2-cyclin B.
Human immunodeficiency virus type 1 (HIV-1) vpr inhibits the replication of tumor cell lines and peripheral blood mononuclear cells. Here it is demonstrated that expression of vpr, either in the context of a provirus or from an independent genetic element, induces a discrete cell cycle arrest, with cells containing 4N DNA. Low cyclin B-associated kinase activity, as well as the status of p34cdc2 and cdc25C phosphorylation, indicates that the cascade of reactions which drives the cell into mitosis has not been initiated. The phosphatase inhibitor okadaic acid releases the block, suggesting that Vpr perturbs upstream regulatorsof the G2-M transition. These studies demonstrate that HIV-1 vpr has profound effects on the cellular factors which control entry into mitosis and indicate vpr's potential contribution to the cellular pathology associated with HIV-1 infection.
D000818:Animals; D001483:Base Sequence; D016203:CDC2 Protein Kinase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002453:Cell Cycle; D002455:Cell Division; D016213:Cyclins / Q000378:metabolism*; D017931:DNA Primers; D005434:Flow Cytometry; D016195:G2 Phase; D015686:Gene Products, env / Q000096:biosynthesis; D016336:Gene Products, vpr / Q000378:metabolism*; D016334:Genes, vpr; D016655:HIV Core Protein p24 / Q000096:biosynthesis; D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D008322:Mammals; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D014162:Transfection; D054334:Viral Regulatory and Accessory Proteins / Q000096:biosynthesis; D054325:vpr Gene Products, Human Immunodeficiency Virus
D016213:Cyclins; D017931:DNA Primers; D015686:Gene Products, env; D016336:Gene Products, vpr; D016655:HIV Core Protein p24; C074286:VPX protein, Human immunodeficiency virus 2; D054334:Viral Regulatory and Accessory Proteins; D054325:vpr Gene Products, Human Immunodeficiency Virus; D016203:CDC2 Protein Kinase