Newcastle disease virus NP and P proteins induce autophagy via the endoplasmic reticulum stress-related unfolded protein response.
Newcastle disease virus (NDV) can replicate and trigger autophagy in human tumor cells. Our previous study confirmed the critical role of autophagy in NDV infection. Here we studied the role of NDV structural proteins in the induction of autophagy through endoplasmic reticulum (ER) stress-related unfolded protein response (UPR) pathways. Ectopic expression of the NDV nucleocapsid protein (NP) or phosphoprotein (P) was sufficient to induce autophagy. NP or P expression also altered ER homeostasis. The PERK and ATF6 pathways, but not the XBP1 pathway, all of which are components of the UPR, were activated in both NDV-infected and NP or P-transfected cells. Knockdown of PERK or ATF6 inhibited NDV-induced autophagy and reduced the extent of NDV replication. Collectively, these data suggest not only roles for the NDV NP and P proteins in autophagy, but also offer new insights into the mechanisms of NDV-induced autophagy through activation of the ER stress-related UPR pathway.
Department of Avian Infectious Diseases, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai, 200241, P.R. China.|Jiangsu Co-Innovation Center for Prevention of Animal Infectious Diseases and Zoonosis, College of Veterinary Medicine, Yangzhou University, Yangzhou, 225000, P.R. China.
Jing-Hua
JH
Cheng
Department of Avian Infectious Diseases, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai, 200241, P.R. China.
Ying-Jie
YJ
Sun
Department of Avian Infectious Diseases, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai, 200241, P.R. China.|College of Agriculture and Biology, Shanghai Jiaotong University, Shanghai, 200240, P.R. China.
Fan-Qing
FQ
Zhang
Jiangsu Co-Innovation Center for Prevention of Animal Infectious Diseases and Zoonosis, College of Veterinary Medicine, Yangzhou University, Yangzhou, 225000, P.R. China.
Xiao-Rong
XR
Zhang
Department of Avian Infectious Diseases, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai, 200241, P.R. China.
Xv-Sheng
XS
Qiu
Jiangsu Co-Innovation Center for Prevention of Animal Infectious Diseases and Zoonosis, College of Veterinary Medicine, Yangzhou University, Yangzhou, 225000, P.R. China.
Li-Ping
LP
Yu
Jiangsu Co-Innovation Center for Prevention of Animal Infectious Diseases and Zoonosis, College of Veterinary Medicine, Yangzhou University, Yangzhou, 225000, P.R. China.
Yan-Tao
YT
Wu
Department of Avian Infectious Diseases, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai, 200241, P.R. China.
Chan
C
Ding
D051702:Activating Transcription Factor 6 / Q000378:metabolism; D001343:Autophagy / Q000235:genetics; D045744:Cell Line, Tumor; D059865:Endoplasmic Reticulum Stress; D015870:Gene Expression; D006801:Humans; D009522:Newcastle disease virus / Q000502:physiology*; D019590:Nucleocapsid Proteins; D009698:Nucleoproteins / Q000235:genetics / Q000378:metabolism*; D010588:Phagosomes / Q000378:metabolism; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D012326:RNA Splicing; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction; D014162:Transfection; D056811:Unfolded Protein Response; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*; D014779:Virus Replication; D000071717:X-Box Binding Protein 1 / Q000235:genetics; D019892:eIF-2 Kinase / Q000378:metabolism
C497111:ATF6 protein, human; D051702:Activating Transcription Factor 6; D019590:Nucleocapsid Proteins; D009698:Nucleoproteins; D010750:Phosphoproteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D014764:Viral Proteins; D000071717:X-Box Binding Protein 1; C409209:nucleoprotein, Newcastle disease virus; C460640:EIF2AK3 protein, human; D019892:eIF-2 Kinase