title: HIV-1 Vpr induces defects in mitosis, cytokinesis, nuclear structure, and centrosomes.
abstract: Human immunodeficiency virus type 1 (HIV-1) Vpr is a 15-kDa accessory protein that contributes to several steps in the viral replication cycle and promotes virus-associated pathology. Previous studies demonstrated that Vpr inhibits G2/M cell cycle progression in both human cells and in the fission yeast Schizosaccharomyces pombe. Here, we report that, upon induction of vpr expression, fission yeast exhibited numerous defects in the assembly and function of the mitotic spindle. In particular, two spindle pole body proteins, sad1p and the polo kinase plo1p, were delocalized in vpr-expressing yeast cells, suggesting that spindle pole body integrity was perturbed. In addition, nuclear envelope structure, contractile actin ring formation, and cytokinesis were also disrupted. Similar Vpr-induced defects in mitosis and cytokinesis were observed in human cells, including aberrant mitotic spindles, multiple centrosomes, and multinucleate cells. These defects in cell division and centrosomes might account for some of the pathological effects associated with HIV-1 infection.
authors.affiliation: Department of Microbiology, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA.
authors.forename: Fred
authors.initials: F
authors.lastname: Chang
authors.forename: Fabio
authors.initials: F
authors.lastname: Re
authors.forename: Sarah
authors.initials: S
authors.lastname: Sebastian
authors.forename: Shelley
authors.initials: S
authors.lastname: Sazer
authors.forename: Jeremy
authors.initials: J
authors.lastname: Luban
mesh_terms: D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000378:metabolism; D002455:Cell Division; D002467:Cell Nucleus / Q000378:metabolism*; D002478:Cells, Cultured; D018385:Centrosome / Q000378:metabolism*; D064447:Checkpoint Kinase 2; D029721:Drosophila Proteins / Q000378:metabolism; D016195:G2 Phase; D016336:Gene Products, vpr / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D008938:Mitosis; D009154:Mutation; D010957:Plasmids / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D012568:Schizosaccharomyces; D008941:Spindle Apparatus; D013997:Time Factors; D014162:Transfection; D014471:Umbilical Veins / Q000166:cytology
chemical_list: D018797:Cell Cycle Proteins; D029721:Drosophila Proteins; D016336:Gene Products, vpr; D029701:Saccharomyces cerevisiae Proteins; D064447:Checkpoint Kinase 2; D017346:Protein Serine-Threonine Kinases; C067022:RAD53 protein, S cerevisiae