title: The human immunodeficiency virus type 1 vpr gene arrests infected T cells in the G2 + M phase of the cell cycle.
abstract: Human immunodeficiency virus type 1 (HIV-1) infection causes profound immunological defects in afflicted patients. Various mechanisms have been proposed to account for the immune dysfunction in AIDS ultimately leading to loss of CD4+ T cells, including HIV-1 envelope-mediated syncytium formation, apoptosis, and cytokine modulation. Here we present results which suggest a novel hypothesis for T-cell dysfunction. We show, using HIV-1 bearing a novel cell surface reporter gene, that infected cells are unable to progress normally through the cell cycle and became arrested in the G2 + M phase. Furthermore, we identify the HIV-1 vpr gene product as being both necessary and sufficient for eliciting this cell cycle arrest. Cell cycle arrest induced by Vpr correlates with an increase in the hyperphosphorylated (inactive) form of the cyclin-dependent serine/threonine kinase CDC2, consistent with an arrest of cells at the boundary of G2 and M.
authors.affiliation: Department of Microbiology & Immunology, UCLA School of Medicine 90095-1678, USA.
authors.forename: J B
authors.initials: JB
authors.lastname: Jowett
authors.forename: V
authors.initials: V
authors.lastname: Planelles
authors.forename: B
authors.initials: B
authors.lastname: Poon
authors.forename: N P
authors.initials: NP
authors.lastname: Shah
authors.forename: M L
authors.initials: ML
authors.lastname: Chen
authors.forename: I S
authors.initials: IS
authors.lastname: Chen
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology; D000595:Amino Acid Sequence; D018791:CD4 Lymphocyte Count; D002453:Cell Cycle; D004247:DNA / Q000032:analysis; D016195:G2 Phase; D016336:Gene Products, vpr / Q000096:biosynthesis / Q000737:chemistry; D016334:Genes, vpr; D015497:HIV-1 / Q000235:genetics* / Q000472:pathogenicity; D006367:HeLa Cells; D006801:Humans; D008228:Lymphoma, Non-Hodgkin; D008938:Mitosis; D008969:Molecular Sequence Data; D016296:Mutagenesis; D016366:Open Reading Frames; D013601:T-Lymphocytes / Q000166:cytology* / Q000473:pathology / Q000821:virology*; D014407:Tumor Cells, Cultured; D054325:vpr Gene Products, Human Immunodeficiency Virus
chemical_list: D016336:Gene Products, vpr; D054325:vpr Gene Products, Human Immunodeficiency Virus; D004247:DNA