A SARS-CoV protein, ORF-6, induces caspase-3 mediated, ER stress and JNK-dependent apoptosis.
Severe acute respiratory syndrome (SARS) coronavirus (CoV) spread from China to more than 30 countries, causing severe outbreaks of atypical pneumonia and over 800 deaths worldwide. CoV primarily infects the upper respiratory and gastrointestinal tract; however, SARS-CoV has a unique pathogenesis because it infects both the upper and lower respiratory tracts and leads to human respiratory diseases. SARS-CoV genome has shown containing 14 open reading frames (ORFs) and 8 of them encode novel proteins. Previous reports show that overexpression of ORF-3a, ORF-3b and ORF-7a induce apoptosis. In this report, we demonstrate that overexpression of ORF-6 also induces apoptosis and that Caspase-3 inhibitor and JNK inhibitor block ORF-6 induced apoptosis. Importantly, the protein level of ER chaperon protein, GRP94, was up-regulated when ORF-6 was overexpressed. All these data suggest that ORF-6 induces apoptosis via Caspase-3 mediated, ER stress and JNK-dependent pathways.
Ye
Zhongde
Z
Department of Biology, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong SAR, China.
Wong
Chung Kai
CK
Li
Peng
P
Xie
Yong
Y
D000818:Animals; D017209:Apoptosis; D053148:Caspase 3 / Q000502:physiology*; D002522:Chlorocebus aethiops; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D004789:Enzyme Activation; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*; D008565:Membrane Proteins / Q000096:biosynthesis; D018832:Molecular Chaperones / Q000096:biosynthesis; D009842:Oligopeptides / Q000494:pharmacology; D015854:Up-Regulation; D014763:Viral Matrix Proteins / Q000037:antagonists & inhibitors / Q000502:physiology; D014764:Viral Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis*
D018840:HSP70 Heat-Shock Proteins; D008565:Membrane Proteins; D018832:Molecular Chaperones; D009842:Oligopeptides; D014763:Viral Matrix Proteins; D014764:Viral Proteins; C516668:benzyloxycarbonyl-aspartyl(OMe)-isoleucyl-prolyl-aspartyl(OMe) fluoromethylketone; C018551:glucose-regulated proteins; C507223:protein 6, SARS virus; C488151:sars7a protein, SARS virus; D048031:JNK Mitogen-Activated Protein Kinases; D053148:Caspase 3