Triggering unfolded protein response by 2-Deoxy-D-glucose inhibits porcine epidemic diarrhea virus propagation.
Identifieur interne : 000482 ( PubMed/Corpus ); précédent : 000481; suivant : 000483Triggering unfolded protein response by 2-Deoxy-D-glucose inhibits porcine epidemic diarrhea virus propagation.
Auteurs : Yue Wang ; Jia-Rong Li ; Ming-Xia Sun ; Bo Ni ; Changchao Huan ; Li Huang ; Chen Li ; Hong-Jie Fan ; Xiao-Feng Ren ; Xiang MaoSource :
- Antiviral research [ 1872-9096 ] ; 2014.
English descriptors
- KwdEn :
- Animals, Antiviral Agents (metabolism), Blotting, Western, Chlorocebus aethiops, Deoxyglucose (metabolism), Endoplasmic Reticulum (ultrastructure), Microscopy, Electron, Transmission, Porcine epidemic diarrhea virus (drug effects), Porcine epidemic diarrhea virus (physiology), Reverse Transcriptase Polymerase Chain Reaction, Unfolded Protein Response (drug effects), Vero Cells, Viral Plaque Assay, Virus Assembly (drug effects), Virus Replication (drug effects).
- MESH :
- chemical , metabolism : Antiviral Agents, Deoxyglucose.
- drug effects : Porcine epidemic diarrhea virus, Unfolded Protein Response, Virus Assembly, Virus Replication.
- physiology : Porcine epidemic diarrhea virus.
- ultrastructure : Endoplasmic Reticulum.
- Animals, Blotting, Western, Chlorocebus aethiops, Microscopy, Electron, Transmission, Reverse Transcriptase Polymerase Chain Reaction, Vero Cells, Viral Plaque Assay.
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.
DOI: 10.1016/j.antiviral.2014.03.007
PubMed: 24681123
Links to Exploration step
pubmed:24681123Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Triggering unfolded protein response by 2-Deoxy-D-glucose inhibits porcine epidemic diarrhea virus propagation.</title><author><name sortKey="Wang, Yue" sort="Wang, Yue" uniqKey="Wang Y" first="Yue" last="Wang">Yue Wang</name><affiliation><nlm:affiliation>College of Veterinary Medicine, Nanjing Agricultural University, 1 Weigang, Nanjing, Jiangsu Province, 210095, China.</nlm:affiliation></affiliation></author><author><name sortKey="Li, Jia Rong" sort="Li, Jia Rong" uniqKey="Li J" first="Jia-Rong" last="Li">Jia-Rong Li</name><affiliation><nlm:affiliation>College of Veterinary Medicine, Nanjing Agricultural University, 1 Weigang, Nanjing, Jiangsu Province, 210095, China.</nlm:affiliation></affiliation></author><author><name sortKey="Sun, Ming Xia" sort="Sun, Ming Xia" uniqKey="Sun M" first="Ming-Xia" last="Sun">Ming-Xia Sun</name><affiliation><nlm:affiliation>College of Veterinary Medicine, Nanjing Agricultural University, 1 Weigang, Nanjing, Jiangsu Province, 210095, China.</nlm:affiliation></affiliation></author><author><name sortKey="Ni, Bo" sort="Ni, Bo" uniqKey="Ni B" first="Bo" last="Ni">Bo Ni</name><affiliation><nlm:affiliation>College of Veterinary Medicine, Nanjing Agricultural University, 1 Weigang, Nanjing, Jiangsu Province, 210095, China.</nlm:affiliation></affiliation></author><author><name sortKey="Huan, Changchao" sort="Huan, Changchao" uniqKey="Huan C" first="Changchao" last="Huan">Changchao Huan</name><affiliation><nlm:affiliation>College of Veterinary Medicine, Nanjing Agricultural University, 1 Weigang, Nanjing, Jiangsu Province, 210095, China.</nlm:affiliation></affiliation></author><author><name sortKey="Huang, Li" sort="Huang, Li" uniqKey="Huang L" first="Li" last="Huang">Li Huang</name><affiliation><nlm:affiliation>College of Veterinary Medicine, Nanjing Agricultural University, 1 Weigang, Nanjing, Jiangsu Province, 210095, China.</nlm:affiliation></affiliation></author><author><name sortKey="Li, Chen" sort="Li, Chen" uniqKey="Li C" first="Chen" last="Li">Chen Li</name><affiliation><nlm:affiliation>College of Veterinary Medicine, Nanjing Agricultural University, 1 Weigang, Nanjing, Jiangsu Province, 210095, China.</nlm:affiliation></affiliation></author><author><name sortKey="Fan, Hong Jie" sort="Fan, Hong Jie" uniqKey="Fan H" first="Hong-Jie" last="Fan">Hong-Jie Fan</name><affiliation><nlm: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.</nlm:affiliation></affiliation></author><author><name sortKey="Ren, Xiao Feng" sort="Ren, Xiao Feng" uniqKey="Ren X" first="Xiao-Feng" last="Ren">Xiao-Feng Ren</name><affiliation><nlm:affiliation>College of Veterinary Medicine, Northeast Agricultural University, 59 Mucai Street, Harbin, Xiangfang District, 150030, China. 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Electronic address: xmao@njau.edu.cn.</nlm:affiliation></affiliation></author></analytic><series><title level="j">Antiviral research</title><idno type="eISSN">1872-9096</idno><imprint><date when="2014" type="published">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Antiviral Agents (metabolism)</term><term>Blotting, Western</term><term>Chlorocebus aethiops</term><term>Deoxyglucose (metabolism)</term><term>Endoplasmic Reticulum (ultrastructure)</term><term>Microscopy, Electron, Transmission</term><term>Porcine epidemic diarrhea virus (drug effects)</term><term>Porcine epidemic diarrhea virus (physiology)</term><term>Reverse Transcriptase Polymerase Chain Reaction</term><term>Unfolded Protein Response (drug effects)</term><term>Vero Cells</term><term>Viral Plaque Assay</term><term>Virus Assembly (drug effects)</term><term>Virus Replication (drug effects)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Antiviral Agents</term><term>Deoxyglucose</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Porcine epidemic diarrhea virus</term><term>Unfolded Protein Response</term><term>Virus Assembly</term><term>Virus Replication</term></keywords><keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>Porcine epidemic diarrhea virus</term></keywords><keywords scheme="MESH" qualifier="ultrastructure" xml:lang="en"><term>Endoplasmic Reticulum</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Blotting, Western</term><term>Chlorocebus aethiops</term><term>Microscopy, Electron, Transmission</term><term>Reverse Transcriptase Polymerase Chain Reaction</term><term>Vero Cells</term><term>Viral Plaque Assay</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">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. </div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">24681123</PMID><DateCompleted><Year>2014</Year><Month>12</Month><Day>19</Day></DateCompleted><DateRevised><Year>2020</Year><Month>04</Month><Day>07</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1872-9096</ISSN><JournalIssue CitedMedium="Internet"><Volume>106</Volume><PubDate><Year>2014</Year><Month>Jun</Month></PubDate></JournalIssue><Title>Antiviral research</Title><ISOAbbreviation>Antiviral Res.</ISOAbbreviation></Journal><ArticleTitle>Triggering unfolded protein response by 2-Deoxy-D-glucose inhibits porcine epidemic diarrhea virus propagation.</ArticleTitle><Pagination><MedlinePgn>33-41</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1016/j.antiviral.2014.03.007</ELocationID><ELocationID EIdType="pii" ValidYN="Y">S0166-3542(14)00081-3</ELocationID><Abstract><AbstractText>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. </AbstractText><CopyrightInformation>Copyright © 2014 Elsevier B.V. All rights reserved.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Wang</LastName><ForeName>Yue</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>College of Veterinary Medicine, Nanjing Agricultural University, 1 Weigang, Nanjing, Jiangsu Province, 210095, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Li</LastName><ForeName>Jia-rong</ForeName><Initials>JR</Initials><AffiliationInfo><Affiliation>College of Veterinary Medicine, Nanjing Agricultural University, 1 Weigang, Nanjing, Jiangsu Province, 210095, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Sun</LastName><ForeName>Ming-xia</ForeName><Initials>MX</Initials><AffiliationInfo><Affiliation>College of Veterinary Medicine, Nanjing Agricultural University, 1 Weigang, Nanjing, Jiangsu Province, 210095, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ni</LastName><ForeName>Bo</ForeName><Initials>B</Initials><AffiliationInfo><Affiliation>College of Veterinary Medicine, Nanjing Agricultural University, 1 Weigang, Nanjing, Jiangsu Province, 210095, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Huan</LastName><ForeName>Changchao</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>College of Veterinary Medicine, Nanjing Agricultural University, 1 Weigang, Nanjing, Jiangsu Province, 210095, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Huang</LastName><ForeName>Li</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>College of Veterinary Medicine, Nanjing Agricultural University, 1 Weigang, Nanjing, Jiangsu Province, 210095, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Li</LastName><ForeName>Chen</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>College of Veterinary Medicine, Nanjing Agricultural University, 1 Weigang, Nanjing, Jiangsu Province, 210095, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Fan</LastName><ForeName>Hong-jie</ForeName><Initials>HJ</Initials><AffiliationInfo><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.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ren</LastName><ForeName>Xiao-feng</ForeName><Initials>XF</Initials><AffiliationInfo><Affiliation>College of Veterinary Medicine, Northeast Agricultural University, 59 Mucai Street, Harbin, Xiangfang District, 150030, China. Electronic address: rxfemail@gmail.com.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Mao</LastName><ForeName>Xiang</ForeName><Initials>X</Initials><AffiliationInfo><Affiliation>College of Veterinary Medicine, Nanjing Agricultural University, 1 Weigang, Nanjing, Jiangsu Province, 210095, China. Electronic address: xmao@njau.edu.cn.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2014</Year><Month>03</Month><Day>25</Day></ArticleDate></Article><MedlineJournalInfo><Country>Netherlands</Country><MedlineTA>Antiviral Res</MedlineTA><NlmUniqueID>8109699</NlmUniqueID><ISSNLinking>0166-3542</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D000998">Antiviral Agents</NameOfSubstance></Chemical><Chemical><RegistryNumber>9G2MP84A8W</RegistryNumber><NameOfSubstance UI="D003847">Deoxyglucose</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000998" MajorTopicYN="N">Antiviral Agents</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D015153" MajorTopicYN="N">Blotting, Western</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D002522" MajorTopicYN="N">Chlorocebus aethiops</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D003847" MajorTopicYN="N">Deoxyglucose</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D004721" MajorTopicYN="N">Endoplasmic Reticulum</DescriptorName><QualifierName UI="Q000648" MajorTopicYN="N">ultrastructure</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D046529" MajorTopicYN="N">Microscopy, Electron, Transmission</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D053485" MajorTopicYN="N">Porcine epidemic diarrhea virus</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="Y">drug effects</QualifierName><QualifierName UI="Q000502" MajorTopicYN="Y">physiology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D020133" MajorTopicYN="N">Reverse Transcriptase Polymerase Chain Reaction</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D056811" MajorTopicYN="N">Unfolded Protein Response</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="Y">drug effects</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D014709" MajorTopicYN="N">Vero Cells</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D010948" MajorTopicYN="N">Viral Plaque Assay</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D019065" MajorTopicYN="N">Virus Assembly</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D014779" MajorTopicYN="N">Virus 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