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PMID: 14767062 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

HIV-1 Vpr induces defects in mitosis, cytokinesis, nuclear structure, and centrosomes.

Molecular biology of the cell ·Vol. 15 ·No. 4 ·2004-04-00 ·Pages 1793-801

Chang F, Re F, Sebastian S, Sazer S, Luban J

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.

MeSH Terms
Cell Cycle Cell Cycle Proteins/metabolism Cell Division Cell Nucleus/metabolism Cells, Cultured Centrosome/metabolism Checkpoint Kinase 2 Drosophila Proteins/metabolism G2 Phase Gene Products, vpr/physiology HeLa Cells Humans Mitosis Mutation Plasmids/metabolism Protein Serine-Threonine Kinases/metabolism Saccharomyces cerevisiae Proteins/metabolism Schizosaccharomyces Spindle Apparatus Time Factors Transfection Umbilical Veins/cytology
Chemicals
Cell Cycle Proteins Drosophila Proteins Gene Products, vpr Saccharomyces cerevisiae Proteins Checkpoint Kinase 2 Protein Serine-Threonine Kinases RAD53 protein, S cerevisiae
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Chang Fred
Department of Microbiology, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA.
Re Fabio
Sebastian Sarah
Sazer Shelley
Luban Jeremy
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Article Info
Journal
Molecular biology of the cell
Abbr.
Mol Biol Cell
ISSN
1059-1524
DOI
10.1091/mbc.e03-09-0691
Published
2004-04-00
Epub
2004-00-06
Pages
1793-801
Language
English
Region
United States
NLM ID
9201390
PMCID
PMC379276
Subset
IM
Grants
NIGMS NIH HHS · GM-49119 · United States
NIAID NIH HHS · AI42848 · United States
NIAID NIH HHS · AI-41857 · United States
NIAID NIH HHS · R01 AI041857 · United States
NIGMS NIH HHS · R01 GM056836 · United States
NIAID NIH HHS · P30 AI042848 · United States
NIGMS NIH HHS · GM-56836 · United States
External Links
PubMed source DOI: 10.1091/mbc.e03-09-0691 PMC Full Text View journal details
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