Phosphorylation of PI3K/Akt and MAPK/ERK in an early entry step of enterovirus 71.
Viruses have been known to subvert the anti-apoptotic pathways of the host cell in order to delay apoptosis. However, the mechanisms utilized by enterovirus 71 (EV71) to mediate anti-apoptotic activity remained undetermined. We observed that EV71 infection induced an early activation of both phosphatidylinositol 3-kinase (PI3K)/Akt and MAPK/ERK signaling pathways. The activity of GSK3beta, a downstream target of these pathways, was negatively regulated by the activation of both MAPK/ERK and PI3K/Akt. The phosphorylation of GSK3 could be inhibited by treatment with the specific inhibitors of MAPK/ERK and PI3K/Akt. Other Akt downstream targets, BAD, caspase-9 and the Forkhead transcription factor (FKHR), were not phosphorylated during the course of infection by EV71. We further demonstrated that infection by UV-irradiated, inactivated virus triggered early Akt activation but was insufficient to trigger late Akt activation. These data suggest that with the phosphorylation of MAPK/ERK and PI3K/Akt the subsequent inactivation of GSK3beta is utilized by EV71 as a potential mechanism to delay host cell apoptosis.
Wong
Wen-Rou
WR
Department of Dermatology, Chang Gung Memorial Hospital, 199 Tung-Hwa North Road, Taipei 105, Taiwan.
Chen
Yu-Yun
YY
Yang
Shun-Min
SM
Chen
Yin-Li
YL
Horng
Jim-Tong
JT
D000818:Animals; D015153:Blotting, Western; D053453:Caspase 9; D020169:Caspases / Q000378:metabolism; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D004586:Electrophoresis; D004770:Enterovirus / Q000528:radiation effects; D004769:Enterovirus Infections / Q000201:enzymology* / Q000821:virology; D004789:Enzyme Activation; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D051058:Oncogene Protein v-akt / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010766:Phosphorylation; D014466:Ultraviolet Rays; D014709:Vero Cells; D010948:Viral Plaque Assay; D051025:bcl-Associated Death Protein / Q000378:metabolism
D053453:Caspase 9; D020169:Caspases; D020928:Mitogen-Activated Protein Kinases; D051058:Oncogene Protein v-akt; D019869:Phosphatidylinositol 3-Kinases; D051025:bcl-Associated Death Protein