title: Human parvovirus B19 nonstructural protein (NS1) induces cell cycle arrest at G(1) phase.
abstract: Human parvovirus B19 infects predominantly erythroid precursor cells, leading to inhibition of erythropoiesis. This erythroid cell damage is mediated by the viral nonstructural protein 1 (NS1) through an apoptotic mechanism. We previously demonstrated that B19 virus infection induces G(2) arrest in erythroid UT7/Epo-S1 cells; however, the role of NS1 in regulating cell cycle arrest is unknown. In this report, by using paclitaxel, a mitotic inhibitor, we show that B19 virus infection induces not only G(2) arrest but also G(1) arrest. Interestingly, UV-irradiated B19 virus, which has inactivated the expression of NS1, still harbors the ability to induce G(2) arrest but not G(1) arrest. Furthermore, treatment with caffeine, a G(2) checkpoint inhibitor, abrogated the B19 virus-induced G(2) arrest despite expression of NS1. These results suggest that the B19 virus-induced G(2) arrest is not mediated by NS1 expression. We also found that NS1-transfected UT7/Epo-S1 and 293T cells induced cell cycle arrest at the G(1) phase. These results indicate that NS1 expression plays a critical role in G(1) arrest induced by B19 virus. Furthermore, NS1 expression significantly increased p21/WAF1 expression, a cyclin-dependent kinase inhibitor that induces G(1) arrest. Thus, G(1) arrest mediated by NS1 may be a prerequisite for the apoptotic damage of erythroid progenitor cells upon B19 virus infection.
authors.affiliation: Department of Microbiology and Immunology, School of Medicine, Tohoku University, Aoba-ku, Sendai, Miyagi 980-8575, Japan.
authors.forename: Eiji
authors.initials: E
authors.lastname: Morita
authors.forename: Akitoshi
authors.initials: A
authors.lastname: Nakashima
authors.forename: Hironobu
authors.initials: H
authors.lastname: Asao
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Sato
authors.forename: Kazuo
authors.initials: K
authors.lastname: Sugamura
mesh_terms: D002453:Cell Cycle / Q000187:drug effects* / Q000502:physiology; D002460:Cell Line; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000378:metabolism; D016193:G1 Phase / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D010322:Parvoviridae Infections / Q000821:virology*; D016732:Parvovirus B19, Human / Q000472:pathogenicity* / Q000528:radiation effects; D015854:Up-Regulation; D017361:Viral Nonstructural Proteins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology
chemical_list: C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; C106202:NS1 protein, parvovirus; D017361:Viral Nonstructural Proteins