title: Human parvovirus B19 induces cell cycle arrest at G(2) phase with accumulation of mitotic cyclins.
abstract: Human parvovirus B19 infects specifically erythroid progenitor cells, which causes transient aplastic crises and hemolytic anemias. Here, we demonstrate that erythroblastoid UT7/Epo cells infected with B19 virus fall into growth arrest with 4N DNA, indicating G(2)/M arrest. These B19 virus-infected cells displayed accumulation of cyclin A, cyclin B1, and phosphorylated cdc2 and were accompanied by an up-regulation in the kinase activity of the cdc2-cyclin B1 complex, similar to that in cells treated with the mitotic inhibitor. However, degradation of nuclear lamina and phosphorylation of histone H3 and H1 were not seen in B19 virus-infected cells, indicating that the infected cells do not enter the M phase. Accumulation of cyclin B1 was persistently localized in the cytoplasm, but not in the nucleus, suggesting that B19 virus infection of erythroid cells raises suppression of nuclear import of cyclin B1, resulting in cell cycle arrest at the G(2) phase. The B19 virus-induced G(2)/M arrest may be the critical event in the damage of erythroid progenitor cells seen in patients with B19 virus infection.
authors.affiliation: Department of Microbiology and Immunology, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan.
authors.forename: E
authors.initials: E
authors.lastname: Morita
authors.forename: K
authors.initials: K
authors.lastname: Tada
authors.forename: H
authors.initials: H
authors.lastname: Chisaka
authors.forename: H
authors.initials: H
authors.lastname: Asao
authors.forename: H
authors.initials: H
authors.lastname: Sato
authors.forename: N
authors.initials: N
authors.lastname: Yaegashi
authors.forename: K
authors.initials: K
authors.lastname: Sugamura
mesh_terms: D016203:CDC2 Protein Kinase / Q000502:physiology; D002453:Cell Cycle; D002460:Cell Line; D016213:Cyclins / Q000502:physiology*; D006801:Humans; D010322:Parvoviridae Infections / Q000378:metabolism* / Q000473:pathology; D016732:Parvovirus B19, Human / Q000502:physiology*; D015398:Signal Transduction; D014779:Virus Replication
chemical_list: D016213:Cyclins; D016203:CDC2 Protein Kinase