title: Newcastle disease virus induces stable formation ofbona fidestress granules to facilitate viral replication through manipulating host protein translation.
abstract: Mammalian cells respond to various environmental stressors to form stress granules (SGs) by arresting cytoplasmic mRNA, protein translation element, and RNA binding proteins. Virus-induced SGs function in different ways, depending on the species of virus; however, the mechanism of SG regulation of virus replication is not well understood. In this study, Newcastle disease virus (NDV) triggered stable formation ofbona fideSGs on HeLa cells through activating the protein kinase R (PKR)/eIF2α pathway. NDV-induced SGs contained classic SG markers T-cell internal antigen (TIA)-1, Ras GTPase-activating protein-binding protein (G3BP)-1, eukaryotic initiation factors, and small ribosomal subunit, which could be disassembled in the presence of cycloheximide. Treatment with nocodazole, a microtubule disruption drug, led to the formation of relatively small and circular granules, indicating that NDV infection induces canonical SGs. Furthermore, the role of SGs on NDV replication was investigated by knockdown of TIA-1 and TIA-1-related (TIAR) protein, the 2 critical components involved in SG formation from the HeLa cells, followed by NDV infection. Results showed that depletion of TIA-1 or TIAR inhibited viral protein synthesis, reduced extracellular virus yields, but increased global protein translation. FISH revealed that NDV-induced SGs contained predominantly cellular mRNA rather than viral mRNA. Deletion of TIA-1 or TIAR reduced NP mRNA levels in polysomes. These results demonstrate that NDV triggers stable formation ofbona fideSGs, which benefit viral protein translation and virus replication by arresting cellular mRNA.-Sun, Y., Dong, L., Yu, S., Wang, X., Zheng, H., Zhang, P., Meng, C., Zhan, Y., Tan, L., Song, C., Qiu, X., Wang, G., Liao, Y., Ding, C. Newcastle disease virus induces stable formation ofbona fidestress granules to facilitate viral replication through manipulating host protein translation.
authors.affiliation: Department of Avian Infectious Diseases, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Science, Shanghai, China.
authors.forename: Yingjie
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Avian Infectious Diseases, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Science, Shanghai, China.|College of Animal Science and Technology, Jilin Agricultural University, Changchun, China.
authors.forename: Luna
authors.initials: L
authors.lastname: Dong
authors.affiliation: Department of Avian Infectious Diseases, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Science, Shanghai, China.
authors.forename: Shengqing
authors.initials: S
authors.lastname: Yu
authors.affiliation: Department of Avian Infectious Diseases, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Science, Shanghai, China.|College of Animal Science and Technology, Anhui Agricultural University, Hefei, China; and.
authors.forename: Xiaoxu
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Avian Infectious Diseases, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Science, Shanghai, China.|College of Animal Science and Technology, Jilin Agricultural University, Changchun, China.
authors.forename: Hang
authors.initials: H
authors.lastname: Zheng
authors.affiliation: Department of Avian Infectious Diseases, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Science, Shanghai, China.
authors.forename: Pin
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Department of Avian Infectious Diseases, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Science, Shanghai, China.
authors.forename: Chunchun
authors.initials: C
authors.lastname: Meng
authors.affiliation: Department of Avian Infectious Diseases, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Science, Shanghai, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhan
authors.affiliation: Department of Avian Infectious Diseases, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Science, Shanghai, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Tan
authors.affiliation: Department of Avian Infectious Diseases, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Science, Shanghai, China.
authors.forename: Cuiping
authors.initials: C
authors.lastname: Song
authors.affiliation: Department of Avian Infectious Diseases, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Science, Shanghai, China.
authors.forename: Xusheng
authors.initials: X
authors.lastname: Qiu
authors.affiliation: College of Animal Science and Technology, Anhui Agricultural University, Hefei, China; and.
authors.forename: Guijun
authors.initials: G
authors.lastname: Wang
authors.affiliation: Department of Avian Infectious Diseases, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Science, Shanghai, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Liao
authors.affiliation: Department of Avian Infectious Diseases, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Science, Shanghai, China; shoveldeen@shvri.ac.cn.|Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, China.
authors.forename: Chan
authors.initials: C
authors.lastname: Ding
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D002478:Cells, Cultured; D002645:Chickens; D003594:Cytoplasmic Granules / Q000378:metabolism*; D004265:DNA Helicases; D015852:Eukaryotic Initiation Factor-2 / Q000378:metabolism; D006367:HeLa Cells; D054884:Host-Pathogen Interactions; D006801:Humans; D009522:Newcastle disease virus / Q000378:metabolism / Q000472:pathogenicity / Q000502:physiology*; D039102:Poly(A)-Binding Proteins / Q000378:metabolism; D000075223:Poly-ADP-Ribose Binding Proteins; D014176:Protein Biosynthesis; D020365:RNA Helicases; D000067776:RNA Recognition Motif Proteins; D016601:RNA-Binding Proteins; D054657:Ribosome Subunits / Q000378:metabolism; D000074019:T-Cell Intracellular Antigen-1; D014779:Virus Replication; D019892:eIF-2 Kinase / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D015852:Eukaryotic Initiation Factor-2; D039102:Poly(A)-Binding Proteins; D000075223:Poly-ADP-Ribose Binding Proteins; D000067776:RNA Recognition Motif Proteins; D016601:RNA-Binding Proteins; D000074019:T-Cell Intracellular Antigen-1; C071558:TIA1 protein, human; C076751:TIAL1 protein, human; D019892:eIF-2 Kinase; D004265:DNA Helicases; C116070:G3BP1 protein, human; D020365:RNA Helicases
keywords: Newcastle disease virus; TIA-1; TIAR; replication; stress granules