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Journal of Virology, August 2001, p. 7555-7563, Vol. 75, No. 16
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.16.7555-7563.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Human Parvovirus B19 Induces Cell Cycle Arrest at G2 Phase with Accumulation of Mitotic Cyclins

Eiji Morita,1 Kotaro Tada,1 Hiroshi Chisaka,2 Hironobu Asao,1 Hiroyuki Sato,3 Nobuo Yaegashi,2 and Kazuo Sugamura1,4,*

Department of Microbiology and Immunology1 and Department of Obstetrics and Gynecology,2 Tohoku University Graduate School of Medicine, and CREST Program of the Japan Science and Technology Corporation,4 Sendai 980-8575, and Fukuoka Red Cross Blood Center, Fukuoka 818-8588,3 Japan

Received 26 March 2001/Accepted 23 May 2001

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 G2/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 G2 phase. The B19 virus-induced G2/M arrest may be the critical event in the damage of erythroid progenitor cells seen in patients with B19 virus infection.

* Corresponding author. Mailing address: Department of Microbiology and Immunology, Tohoku University School of Medicine, 21- Seiryo-machi, Aoba-ku, Sendai 980-9575, Japan. Phone: 81-22-717-8096. Fax: 81-22-717-8097. E-mail: sugamura{at}mail.cc.tohoku.ac.jp.

Journal of Virology, August 2001, p. 7555-7563, Vol. 75, No. 16
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.16.7555-7563.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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