title: AMP-activated protein kinase facilitates avian reovirus to induce mitogen-activated protein kinase (MAPK) p38 and MAPK kinase 3/6 signalling that is beneficial for virus replication.
abstract: Stimulated by energetic stress, AMP-activated protein kinase (AMPK) controls several cellular functions. It was discovered here that infection of Vero cells with avian reovirus (ARV) upregulated AMPK and mitogen-activated protein kinase (MAPK) p38 phosphorylation in a time- and dose-dependent manner. Being an energy status sensor, AMPK is potentially an upstream regulator of MAPK p38. Treatment with 5-amino-4-imidazolecarboxamide ribose (AICAR), a well-known activator of AMPK, induced phosphorylation of MAPK p38. Unlike AICAR, wortmannin or rapamycin did not induce phosphorylation of MAPK p38, suggesting that mTOR inhibition is not a determining factor in MAPK p38 phosphorylation. Inhibition of AMPK by compound C antagonized the effect of AICAR on MAPK p38 in Vero cells. Specific inhibition of AMPK by small interfering RNA or compound C also suppressed ARV-induced phosphorylation of MAPK kinase (MKK) 3/6 and MAPK p38 in Vero and DF-1 cells, thereby providing a link between AMPK signalling and the MAPK p38 pathway. The mechanism of ARV-enhanced phosphorylation of MKK 3/6 and MAPK p38 in cells was not merely due to glucose deprivation, a probable activator of AMPK. In the current study, direct inhibition of MAPK p38 by SB202190 decreased the level of ARV-induced syncytium formation in Vero and DF-1 cells, and decreased the protein levels of ARV sigma A and sigma C and the progeny titre of ARV, suggesting that activation of MAPK p38 is beneficial for ARV replication. Taken together, these results suggested that AMPK could facilitate MKK 3/6 and MAPK p38 signalling that is beneficial for ARV replication. Although well studied in energy metabolism, this study provides evidence for the first time that AMPK plays a role in modulating ARV and host-cell interaction.
authors: Department of Veterinary Medicine, National Pingtung University of Science and Technology, Pingtung 912, Taiwan, ROC.
authors: Wen T
authors: WT
authors: Ji
authors: Department of Veterinary Medicine, National Chung-Hsing University, Taichung, Taiwan, ROC.
authors: Long H
authors: LH
authors: Lee
authors: Department of Pharmacy, Tajen University of Science and Technology, Pingtung 912, Taiwan, ROC.|Department of Veterinary Medicine, National Pingtung University of Science and Technology, Pingtung 912, Taiwan, ROC.
authors: Feng L
authors: FL
authors: Lin
authors: Graduate Institute of Biotechnology, National Pingtung University of Science and Technology, Pingtung 912, Taiwan, ROC.
authors: Lai
authors: L
authors: Wang
authors: Graduate Institute of Biotechnology, National Pingtung University of Science and Technology, Pingtung 912, Taiwan, ROC.|Department of Veterinary Medicine, National Pingtung University of Science and Technology, Pingtung 912, Taiwan, ROC.
authors: Hung J
authors: HJ
authors: Liu
mesh_terms: D000091162:AMP-Activated Protein Kinase Kinases; D000818:Animals; D002642:Chick Embryo / Q000821:virology; D002522:Chlorocebus aethiops; D004789:Enzyme Activation; D005347:Fibroblasts / Q000821:virology*; D054884:Host-Pathogen Interactions; D048371:MAP Kinase Kinase 3 / Q000378:metabolism*; D030101:Orthoreovirus, Avian / Q000201:enzymology / Q000472:pathogenicity / Q000502:physiology*; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism*; D015398:Signal Transduction; D014709:Vero Cells / Q000821:virology; D014779:Virus Replication; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D011494:Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D000091162:AMP-Activated Protein Kinase Kinases; D048371:MAP Kinase Kinase 3