Department of Medicine, University of Calgary, Calgary, AB, Canada.
J Virol Methods. 2010 Dec;170(1-2):21-9. doi: 10.1016/j.jviromet.2010.08.014. Epub 2010 Sep 8.
BK polyomavirus causes disease in immunosuppressed patients. BK virus replication was augmented in HEL-299 cells cultured in conditions that activated the MAP kinase, ERK1/2. To determine if MAP kinase activation increased BK virus replication, cells were treated with serum and phorbol 12-myristate 13-acetate (PMA). Serum and PMA stimulated large T-antigen expression and increased BK virus DNA replication. The effects of serum/PMA were directly related to MAP kinase signal activation since viral replication was reduced by the MEK1/2 inhibitor U0126. PMA also increased cyclin D1 expression and inhibition of cyclin D1/CDK4 complex and the cell cycle reduced BK virus infection. The PMA effect occurred independent of direct transcriptional activation of the viral NCCR. In HEL-299 cells, virus infection in high serum and PMA accelerated viral replication that resulted, within 7 days, in the production of high titer infectious BK virus. These results show that MAP kinase signal activation increases BK virus replication.
BK 多瘤病毒会导致免疫抑制患者发病。在激活丝裂原活化蛋白激酶（MAPK）ERK1/2 的条件下培养的 HEL-299 细胞中，BK 病毒复制得到增强。为了确定 MAPK 激活是否会增加 BK 病毒的复制，用血清和佛波醇 12-肉豆蔻酸 13-乙酸酯（PMA）处理细胞。血清和 PMA 刺激大 T 抗原表达并增加 BK 病毒 DNA 复制。血清/PMA 的作用与 MAPK 信号的激活直接相关，因为 MEK1/2 抑制剂 U0126 降低了病毒复制。PMA 还增加了细胞周期蛋白 D1 的表达，并抑制了细胞周期蛋白 D1/CDK4 复合物，从而减少了 BK 病毒的感染。PMA 的作用不依赖于病毒 NCCR 的直接转录激活。在 HEL-299 细胞中，高血清和 PMA 中的病毒感染加速了病毒复制，在 7 天内产生了高滴度的传染性 BK 病毒。这些结果表明，MAPK 信号的激活增加了 BK 病毒的复制。
