PLK1 down-regulates parainfluenza virus 5 gene expression.
The paramyxoviruses are a family of negative-sense RNA viruses that includes many important human and animal pathogens. Paramyxovirus RNA synthesis requires the viral phosphoprotein (P) and the large (L) protein. Phosphorylation of P is thought to regulate viral gene expression, though direct proof remains elusive. Recently, we reported that phosphorylation of a specific residue (Ser157) of the P protein of parainfluenza virus 5 (PIV5), a prototypical paramyxovirus, correlates with decreased viral gene expression and cytokine expression in infected cells. Here, we show that: Polo-like kinase 1 (PLK1), a serine/theronine kinase that plays a critical role in regulating the cell cycle, interacts with PIV5 P through the S157 residue; PLK1 inhibition increases viral gene expression; PLK1 over-expression inhibits viral gene expression; and PLK1 directly phosphorylates P in vitro, indicating that PLK1 down-regulates viral gene expression by phosphorylating P. Furthermore, we have determined the PLK1 phosphorylation site on P and found that mutant recombinant PIV5 whose P proteins cannot either bind to or be phosphorylated by PLK1 have similar phenotypes. Increased viral gene expression in PIV5 with mutations in the PLK1 binding/phosphorylation sites correlates with increased induction of cell death and cytokine expression, suggesting that PIV5 limits its viral gene expression to avoid these host effects. It is possible that targeting PLK1 will enhance host innate immune responses, leading to a novel strategy of clearing paramyxovirus infections quickly.
Sun
Dengyun
D
Intercollege Graduate Program in Cell and Developmental Biology, Pennsylvania State University, University Park, Pennsylvania, USA.
Luthra
Priya
P
Li
Zhuo
Z
He
Biao
B
D020816:Amino Acid Motifs; D019943:Amino Acid Substitution; D017209:Apoptosis / Q000502:physiology; D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D015536:Down-Regulation; D015967:Gene Expression Regulation, Viral / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D045402:Parainfluenza Virus 5 / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011621:Pteridines / Q000494:pharmacology; D018108:Respirovirus / Q000235:genetics* / Q000378:metabolism; D010253:Respirovirus Infections / Q000378:metabolism*; D014162:Transfection; D014764:Viral Proteins / Q000378:metabolism; D000097869:Polo-Like Kinase 1
D018797:Cell Cycle Proteins; D016207:Cytokines; D010750:Phosphoproteins; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D011621:Pteridines; D014764:Viral Proteins; D000097869:Polo-Like Kinase 1; C518477:BI 2536; C055859:P protein, Sendai virus