期刊
JOURNAL OF VIROLOGICAL METHODS
卷 170, 期 1-2, 页码 21-29出版社
ELSEVIER
DOI: 10.1016/j.jviromet.2010.08.014
关键词
BK polyomavirus; Mitogen-activated protein kinase; Cell cycle; Kidney transplantation
资金
- Canadian Institutes for Health Research
- Canadian Foundation for Innovation
- Alberta Heritage Foundation for Medical Research
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. (C) 2010 Elsevier BM. All rights reserved.
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