Human parvovirus B19 induces cell cycle arrest at G2 phase with accumulation of mitotic cyclins
Human parvovirus B19 induces cell cycle arrest at G2 phase with accumulation of mitotic cyclins
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DOI：
10.1128/jvi.75.16.7555-7563.2001
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发表时间：
2001-08-01
影响因子：
5.4
通讯作者：
Sugamura, K
中科院分区：
文献类型：
--
作者：
Morita, E;Tada, K;Sugamura, K
人类细小病毒 B19 特异性感染红系祖细胞，导致短暂的再生障碍性危象和溶血性贫血。在这里，我们证明感染 B19 病毒的类红细胞 UT7/Epo 细胞因 4N DNA 而陷入生长停滞，表明 G(2)/M 停滞。这些 B19 病毒感染的细胞表现出细胞周期蛋白 A、细胞周期蛋白 B1 和磷酸化 cdc2 的积累，并伴随着 cdc2-细胞周期蛋白 B1 复合物激酶活性的上调，类似于用有丝分裂抑制剂处理的细胞。然而，在B19病毒感染的细胞中没有观察到核纤层的降解以及组蛋白H3和H1的磷酸化，表明感染的细胞没有进入M期。细胞周期蛋白 B1 的积累持续位于细胞质中，但不在细胞核中，表明 B19 病毒感染红系细胞会增强对细胞周期蛋白 B1 核输入的抑制，导致细胞周期停滞在 G(2) 期。 B19 病毒诱导的 G(2)/M 停滞可能是 B19 病毒感染患者红系祖细胞损伤的关键事件。
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 G(2)/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 G(2) phase. The B19 virus-induced G(2)/M arrest may be the critical event in the damage of erythroid progenitor cells seen in patients with B19 virus infection.