MAP kinase activation increases BK polyomavirus replication and facilitates viral propagation in vitro.
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.
Seamone
Mark E
ME
Department of Medicine, University of Calgary, Calgary, AB, Canada.
Wang
Wenjie
W
Acott
Philip
P
Beck
Paul L
PL
Tibbles
Lee Anne
LA
Muruve
Daniel A
DA
D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000378:metabolism; D001739:BK Virus / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D002453:Cell Cycle / Q000187:drug effects; D002522:Chlorocebus aethiops; D019938:Cyclin D1 / Q000378:metabolism; D004789:Enzyme Activation; D005455:Fluorescent Antibody Technique; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D015151:Immunoblotting; D020935:MAP Kinase Signaling System; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D016133:Polymerase Chain Reaction; D044967:Serum; D013755:Tetradecanoylphorbol Acetate / Q000031:analogs & derivatives / Q000494:pharmacology; D014709:Vero Cells; D014775:Virus Activation
D000952:Antigens, Polyomavirus Transforming; D019938:Cyclin D1; C020922:4-O-methyl-12-O-tetradecanoylphorbol 13-acetate; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D013755:Tetradecanoylphorbol Acetate