Human Parvovirus B19 Nonstructural Protein (NS1) Induces Cell Cycle Arrest at G ₁ Phase

• Eiji Morita

  Department of Microbiology and Immunology, School of Medicine, Tohoku University, Aoba-ku, Sendai, Miyagi 980-8575

• Akitoshi Nakashima

  Department of Microbiology and Immunology, School of Medicine, Tohoku University, Aoba-ku, Sendai, Miyagi 980-8575

• Hironobu Asao

  Department of Microbiology and Immunology, School of Medicine, Tohoku University, Aoba-ku, Sendai, Miyagi 980-8575

• Hiroyuki Sato

  Fukuoka Red Cross Blood Center, Fukuoka 818-8588, Japan

• Kazuo Sugamura

  Department of Microbiology and Immunology, School of Medicine, Tohoku University, Aoba-ku, Sendai, Miyagi 980-8575

抄録

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.

収録刊行物

• Journal of Virology

  Journal of Virology 77 (5), 2915-2921, 2003-03

  American Society for Microbiology

キーワード

• Virology
• Insect Science
• Immunology
• Microbiology

詳細情報

• CRID: 1360018298136976384
• NII論文ID: 30020797799
• DOI: 10.1128/jvi.77.5.2915-2921.2003
• ISSN: 10985514
• ISSN: 0022538X
• Web Site: https://journals.asm.org/doi/pdf/10.1128/JVI.77.5.2915-2921.2003
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