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Journal of Virology, March 2003, p. 2915-2921, Vol. 77, No. 5
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.5.2915-2921.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Human Parvovirus B19 Nonstructural Protein (NS1) Induces Cell Cycle Arrest at G₁ Phase

Department of Microbiology and Immunology, School of Medicine, Tohoku University, Aoba-ku, Sendai, Miyagi 980-8575,¹ Fukuoka Red Cross Blood Center, Fukuoka 818-8588, Japan²

Received 3 September 2002/ Accepted 26 November 2002

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 G₂ 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 G₂ arrest but also G₁ arrest. Interestingly, UV-irradiated B19 virus, which has inactivated the expression of NS1, still harbors the ability to induce G₂ arrest but not G₁ arrest. Furthermore, treatment with caffeine, a G₂ checkpoint inhibitor, abrogated the B19 virus-induced G₂ arrest despite expression of NS1. These results suggest that the B19 virus-induced G₂ 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 G₁ phase. These results indicate that NS1 expression plays a critical role in G₁ arrest induced by B19 virus. Furthermore, NS1 expression significantly increased p21/WAF1 expression, a cyclin-dependent kinase inhibitor that induces G₁ arrest. Thus, G₁ arrest mediated by NS1 may be a prerequisite for the apoptotic damage of erythroid progenitor cells upon B19 virus infection.

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