MAP kinase activation increases BK polyomavirus replication and facilitates viral propagation in vitro

作者：Seamone Mark E; Wang Wenjie; Acott Philip; Beck Paul L; Tibbles Lee Anne; Muruve Daniel A^*

来源：Journal of Virological Methods, 2010, 170(1-2): 21-29.

DOI：10.1016/j.jviromet.2010.08.014

• BK polyomavirus
• Mitogen-activated protein kinase
• Cell cycle
• Kidney transplantation

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.

• 出版日期2010-12