title: Influenza A virus replication induces cell cycle arrest in G0/G1 phase.
abstract: Many viruses interact with the host cell division cycle to favor their own growth. In this study, we examined the ability of influenza A virus to manipulate cell cycle progression. Our results show that influenza A virus A/WSN/33 (H1N1) replication results in G(0)/G(1)-phase accumulation of infected cells and that this accumulation is caused by the prevention of cell cycle entry from G(0)/G(1) phase into S phase. Consistent with the G(0)/G(1)-phase accumulation, the amount of hyperphosphorylated retinoblastoma protein, a necessary active form for cell cycle progression through late G(1) into S phase, decreased after infection with A/WSN/33 (H1N1) virus. In addition, other key molecules in the regulation of the cell cycle, such as p21, cyclin E, and cyclin D1, were also changed and showed a pattern of G(0)/G(1)-phase cell cycle arrest. It is interesting that increased viral protein expression and progeny virus production in cells synchronized in the G(0)/G(1) phase were observed compared to those in either unsynchronized cells or cells synchronized in the G(2)/M phase. G(0)/G(1)-phase cell cycle arrest is likely a common strategy, since the effect was also observed in other strains, such as H3N2, H9N2, PR8 H1N1, and pandemic swine H1N1 viruses. These findings, in all, suggest that influenza A virus may provide favorable conditions for viral protein accumulation and virus production by inducing a G(0)/G(1)-phase cell cycle arrest in infected cells.
authors.affiliation: Key Laboratory of Molecular Virology & Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, 225 South Chongqing Road, Shanghai 200025, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: He
authors.forename: Ke
authors.initials: K
authors.lastname: Xu
authors.forename: Bjoern
authors.initials: B
authors.lastname: Keiner
authors.forename: Jianfang
authors.initials: J
authors.lastname: Zhou
authors.forename: Volker
authors.initials: V
authors.lastname: Czudai
authors.forename: Tianxian
authors.initials: T
authors.lastname: Li
authors.forename: Ze
authors.initials: Z
authors.lastname: Chen
authors.forename: Jinhua
authors.initials: J
authors.lastname: Liu
authors.forename: Hans-Dieter
authors.initials: HD
authors.lastname: Klenk
authors.forename: Yue Long
authors.initials: YL
authors.lastname: Shu
authors.forename: Bing
authors.initials: B
authors.lastname: Sun
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology / Q000821:virology; D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D002642:Chick Embryo; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D004285:Dogs; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D016193:G1 Phase / Q000502:physiology*; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000502:physiology*; D053122:Influenza A Virus, H3N2 Subtype / Q000502:physiology*; D053127:Influenza A Virus, H9N2 Subtype / Q000502:physiology*; D009980:Influenza A virus / Q000502:physiology*; D007668:Kidney / Q000166:cytology / Q000378:metabolism / Q000821:virology; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology / Q000821:virology; D008938:Mitosis; D016192:Resting Phase, Cell Cycle / Q000502:physiology*; D014764:Viral Proteins / Q000378:metabolism; D014779:Virus Replication
chemical_list: D014764:Viral Proteins; D018844:Cyclin-Dependent Kinases