title: Triggering unfolded protein response by 2-Deoxy-D-glucose inhibits porcine epidemic diarrhea virus propagation.
abstract: The unfolded protein response (UPR) is cyto-protective machinery elicited towards an influx of large amount of protein synthesis in the endoplasmic reticulum (ER). Extensive studies suggest that the UPR can also be activated during virus infection. In the present studies, we first evaluated if porcine epidemic diarrhea virus (PEDV) infection activated the UPR pathways. Electron microscopy analysis demonstrated the morphology changes of ER post-PEDV infection. Western blot and real-time PCR identified the differences of UPR genes in response to PEDV infection. The results suggested that PEDV infection induced UPR in Vero cells. Meanwhile, we silenced the expression of PKR-like ER kinase (PERK) by shRNA, we found that the knockdown of PERK increased virus loads in the cells, which was consistent with the result on 4-phenylbutyrate (4-PBA) treatment. We next determined whether 2-Deoxy-d-glucose (2-DG), an ER stress inducer, possessed antiviral activity against PEDV infection. Plaque formation assay, RT-PCR and Western blot analysis suggested that 2-DG might inhibit virus infection by affecting viral protein translation during the early stage of virus infection. Interestingly, we also found that 2-DG treatment could affect virus assembly, which is similar to previous studies on influenza virus. All these results support the therapeutic potential of using 2-DG or glucose/mannose analogs to induce the UPR to block virus replication.
authors.affiliation: College of Veterinary Medicine, Nanjing Agricultural University, 1 Weigang, Nanjing, Jiangsu Province, 210095, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Wang
authors.affiliation: College of Veterinary Medicine, Nanjing Agricultural University, 1 Weigang, Nanjing, Jiangsu Province, 210095, China.
authors.forename: Jia-rong
authors.initials: JR
authors.lastname: Li
authors.affiliation: College of Veterinary Medicine, Nanjing Agricultural University, 1 Weigang, Nanjing, Jiangsu Province, 210095, China.
authors.forename: Ming-xia
authors.initials: MX
authors.lastname: Sun
authors.affiliation: College of Veterinary Medicine, Nanjing Agricultural University, 1 Weigang, Nanjing, Jiangsu Province, 210095, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Ni
authors.affiliation: College of Veterinary Medicine, Nanjing Agricultural University, 1 Weigang, Nanjing, Jiangsu Province, 210095, China.
authors.forename: Changchao
authors.initials: C
authors.lastname: Huan
authors.affiliation: College of Veterinary Medicine, Nanjing Agricultural University, 1 Weigang, Nanjing, Jiangsu Province, 210095, China.
authors.forename: Li
authors.initials: L
authors.lastname: Huang
authors.affiliation: College of Veterinary Medicine, Nanjing Agricultural University, 1 Weigang, Nanjing, Jiangsu Province, 210095, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Li
authors.affiliation: College of Veterinary Medicine, Nanjing Agricultural University, 1 Weigang, Nanjing, Jiangsu Province, 210095, China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, 225009, China.
authors.forename: Hong-jie
authors.initials: HJ
authors.lastname: Fan
authors.affiliation: College of Veterinary Medicine, Northeast Agricultural University, 59 Mucai Street, Harbin, Xiangfang District, 150030, China. Electronic address: rxfemail@gmail.com.
authors.forename: Xiao-feng
authors.initials: XF
authors.lastname: Ren
authors.affiliation: College of Veterinary Medicine, Nanjing Agricultural University, 1 Weigang, Nanjing, Jiangsu Province, 210095, China. Electronic address: xmao@njau.edu.cn.
authors.forename: Xiang
authors.initials: X
authors.lastname: Mao
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000378:metabolism*; D015153:Blotting, Western; D002522:Chlorocebus aethiops; D003847:Deoxyglucose / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000648:ultrastructure; D046529:Microscopy, Electron, Transmission; D053485:Porcine epidemic diarrhea virus / Q000187:drug effects* / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D056811:Unfolded Protein Response / Q000187:drug effects*; D014709:Vero Cells; D010948:Viral Plaque Assay; D019065:Virus Assembly / Q000187:drug effects; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D000998:Antiviral Agents; D003847:Deoxyglucose
keywords: 2-Deoxy-d-glucose; Antiviral; Endoplasmic reticulum stress; Porcine epidemic diarrhea virus; Unfolded protein response