Human parvovirus B19 nonstructural protein (NS1) induces cell cycle arrest at G(1) phase.
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.
Morita
Eiji
E
Department of Microbiology and Immunology, School of Medicine, Tohoku University, Aoba-ku, Sendai, Miyagi 980-8575, Japan.
Nakashima
Akitoshi
A
Asao
Hironobu
H
Sato
Hiroyuki
H
Sugamura
Kazuo
K
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
C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; C106202:NS1 protein, parvovirus; D017361:Viral Nonstructural Proteins