The effect of inhibition of PP1 and TNFα signaling on pathogenesis of SARS coronavirus.
Identifieur interne : 000C09 ( PubMed/Corpus ); précédent : 000C08; suivant : 000C10The effect of inhibition of PP1 and TNFα signaling on pathogenesis of SARS coronavirus.
Auteurs : Jason E. Mcdermott ; Hugh D. Mitchell ; Lisa E. Gralinski ; Amie J. Eisfeld ; Laurence Josset ; Armand Bankhead ; Gabriele Neumann ; Susan C. Tilton ; Alexandra Sch Fer ; Chengjun Li ; Shufang Fan ; Shannon Mcweeney ; Ralph S. Baric ; Michael G. Katze ; Katrina M. WatersSource :
- BMC systems biology [ 1752-0509 ] ; 2016.
Abstract
The complex interplay between viral replication and host immune response during infection remains poorly understood. While many viruses are known to employ anti-immune strategies to facilitate their replication, highly pathogenic virus infections can also cause an excessive immune response that exacerbates, rather than reduces pathogenicity. To investigate this dichotomy in severe acute respiratory syndrome coronavirus (SARS-CoV), we developed a transcriptional network model of SARS-CoV infection in mice and used the model to prioritize candidate regulatory targets for further investigation.
DOI: 10.1186/s12918-016-0336-6
PubMed: 27663205
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">The effect of inhibition of PP1 and TNFα signaling on pathogenesis of SARS coronavirus.</title><author><name sortKey="Mcdermott, Jason E" sort="Mcdermott, Jason E" uniqKey="Mcdermott J" first="Jason E" last="Mcdermott">Jason E. Mcdermott</name><affiliation><nlm:affiliation>Computational Biology and Bioinformatics Group, Pacific Northwest National Laboratory, Richland, WA, 99354, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Mitchell, Hugh D" sort="Mitchell, Hugh D" uniqKey="Mitchell H" first="Hugh D" last="Mitchell">Hugh D. Mitchell</name><affiliation><nlm:affiliation>Computational Biology and Bioinformatics Group, Pacific Northwest National Laboratory, Richland, WA, 99354, USA. Hugh.Mitchell@pnnl.gov.</nlm:affiliation></affiliation></author><author><name sortKey="Gralinski, Lisa E" sort="Gralinski, Lisa E" uniqKey="Gralinski L" first="Lisa E" last="Gralinski">Lisa E. Gralinski</name><affiliation><nlm:affiliation>Department of Epidemiology, University of North Carolina Chapel Hill, Chapel Hill, NC, 27599, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Eisfeld, Amie J" sort="Eisfeld, Amie J" uniqKey="Eisfeld A" first="Amie J" last="Eisfeld">Amie J. Eisfeld</name><affiliation><nlm:affiliation>Department of Pathobiological Sciences, School of Veterinary Medicine, Influenza Research Institute, University of Wisconsin-Madison, Madison, WI, 53715, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Josset, Laurence" sort="Josset, Laurence" uniqKey="Josset L" first="Laurence" last="Josset">Laurence Josset</name><affiliation><nlm:affiliation>Department of Microbiology, University of Washington, Seattle, WA, 98195, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Bankhead, Armand" sort="Bankhead, Armand" uniqKey="Bankhead A" first="Armand" last="Bankhead">Armand Bankhead</name><affiliation><nlm:affiliation>Division of Biostatistics, Department of Public Health and Preventive Medicine, Oregon Health and Science University, Portland, OR, 97239, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Neumann, Gabriele" sort="Neumann, Gabriele" uniqKey="Neumann G" first="Gabriele" last="Neumann">Gabriele Neumann</name><affiliation><nlm:affiliation>Department of Pathobiological Sciences, School of Veterinary Medicine, Influenza Research Institute, University of Wisconsin-Madison, Madison, WI, 53715, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Tilton, Susan C" sort="Tilton, Susan C" uniqKey="Tilton S" first="Susan C" last="Tilton">Susan C. Tilton</name><affiliation><nlm:affiliation>Computational Biology and Bioinformatics Group, Pacific Northwest National Laboratory, Richland, WA, 99354, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Sch Fer, Alexandra" sort="Sch Fer, Alexandra" uniqKey="Sch Fer A" first="Alexandra" last="Sch Fer">Alexandra Sch Fer</name><affiliation><nlm:affiliation>Department of Epidemiology, University of North Carolina Chapel Hill, Chapel Hill, NC, 27599, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Li, Chengjun" sort="Li, Chengjun" uniqKey="Li C" first="Chengjun" last="Li">Chengjun Li</name><affiliation><nlm:affiliation>Department of Pathobiological Sciences, School of Veterinary Medicine, Influenza Research Institute, University of Wisconsin-Madison, Madison, WI, 53715, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Fan, Shufang" sort="Fan, Shufang" uniqKey="Fan S" first="Shufang" last="Fan">Shufang Fan</name><affiliation><nlm:affiliation>Department of Pathobiological Sciences, School of Veterinary Medicine, Influenza Research Institute, University of Wisconsin-Madison, Madison, WI, 53715, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Mcweeney, Shannon" sort="Mcweeney, Shannon" uniqKey="Mcweeney S" first="Shannon" last="Mcweeney">Shannon Mcweeney</name><affiliation><nlm:affiliation>Division of Biostatistics, Department of Public Health and Preventive Medicine, Oregon Health and Science University, Portland, OR, 97239, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Baric, Ralph S" sort="Baric, Ralph S" uniqKey="Baric R" first="Ralph S" last="Baric">Ralph S. Baric</name><affiliation><nlm:affiliation>Department of Epidemiology, University of North Carolina Chapel Hill, Chapel Hill, NC, 27599, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Katze, Michael G" sort="Katze, Michael G" uniqKey="Katze M" first="Michael G" last="Katze">Michael G. Katze</name><affiliation><nlm:affiliation>Department of Microbiology, University of Washington, Seattle, WA, 98195, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Waters, Katrina M" sort="Waters, Katrina M" uniqKey="Waters K" first="Katrina M" last="Waters">Katrina M. Waters</name><affiliation><nlm:affiliation>Computational Biology and Bioinformatics Group, Pacific Northwest National Laboratory, Richland, WA, 99354, USA.</nlm:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2016">2016</date><idno type="RBID">pubmed:27663205</idno><idno type="pmid">27663205</idno><idno type="doi">10.1186/s12918-016-0336-6</idno><idno type="wicri:Area/PubMed/Corpus">000C09</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000C09</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">The effect of inhibition of PP1 and TNFα signaling on pathogenesis of SARS coronavirus.</title><author><name sortKey="Mcdermott, Jason E" sort="Mcdermott, Jason E" uniqKey="Mcdermott J" first="Jason E" last="Mcdermott">Jason E. Mcdermott</name><affiliation><nlm:affiliation>Computational Biology and Bioinformatics Group, Pacific Northwest National Laboratory, Richland, WA, 99354, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Mitchell, Hugh D" sort="Mitchell, Hugh D" uniqKey="Mitchell H" first="Hugh D" last="Mitchell">Hugh D. Mitchell</name><affiliation><nlm:affiliation>Computational Biology and Bioinformatics Group, Pacific Northwest National Laboratory, Richland, WA, 99354, USA. Hugh.Mitchell@pnnl.gov.</nlm:affiliation></affiliation></author><author><name sortKey="Gralinski, Lisa E" sort="Gralinski, Lisa E" uniqKey="Gralinski L" first="Lisa E" last="Gralinski">Lisa E. Gralinski</name><affiliation><nlm:affiliation>Department of Epidemiology, University of North Carolina Chapel Hill, Chapel Hill, NC, 27599, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Eisfeld, Amie J" sort="Eisfeld, Amie J" uniqKey="Eisfeld A" first="Amie J" last="Eisfeld">Amie J. Eisfeld</name><affiliation><nlm:affiliation>Department of Pathobiological Sciences, School of Veterinary Medicine, Influenza Research Institute, University of Wisconsin-Madison, Madison, WI, 53715, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Josset, Laurence" sort="Josset, Laurence" uniqKey="Josset L" first="Laurence" last="Josset">Laurence Josset</name><affiliation><nlm:affiliation>Department of Microbiology, University of Washington, Seattle, WA, 98195, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Bankhead, Armand" sort="Bankhead, Armand" uniqKey="Bankhead A" first="Armand" last="Bankhead">Armand Bankhead</name><affiliation><nlm:affiliation>Division of Biostatistics, Department of Public Health and Preventive Medicine, Oregon Health and Science University, Portland, OR, 97239, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Neumann, Gabriele" sort="Neumann, Gabriele" uniqKey="Neumann G" first="Gabriele" last="Neumann">Gabriele Neumann</name><affiliation><nlm:affiliation>Department of Pathobiological Sciences, School of Veterinary Medicine, Influenza Research Institute, University of Wisconsin-Madison, Madison, WI, 53715, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Tilton, Susan C" sort="Tilton, Susan C" uniqKey="Tilton S" first="Susan C" last="Tilton">Susan C. Tilton</name><affiliation><nlm:affiliation>Computational Biology and Bioinformatics Group, Pacific Northwest National Laboratory, Richland, WA, 99354, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Sch Fer, Alexandra" sort="Sch Fer, Alexandra" uniqKey="Sch Fer A" first="Alexandra" last="Sch Fer">Alexandra Sch Fer</name><affiliation><nlm:affiliation>Department of Epidemiology, University of North Carolina Chapel Hill, Chapel Hill, NC, 27599, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Li, Chengjun" sort="Li, Chengjun" uniqKey="Li C" first="Chengjun" last="Li">Chengjun Li</name><affiliation><nlm:affiliation>Department of Pathobiological Sciences, School of Veterinary Medicine, Influenza Research Institute, University of Wisconsin-Madison, Madison, WI, 53715, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Fan, Shufang" sort="Fan, Shufang" uniqKey="Fan S" first="Shufang" last="Fan">Shufang Fan</name><affiliation><nlm:affiliation>Department of Pathobiological Sciences, School of Veterinary Medicine, Influenza Research Institute, University of Wisconsin-Madison, Madison, WI, 53715, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Mcweeney, Shannon" sort="Mcweeney, Shannon" uniqKey="Mcweeney S" first="Shannon" last="Mcweeney">Shannon Mcweeney</name><affiliation><nlm:affiliation>Division of Biostatistics, Department of Public Health and Preventive Medicine, Oregon Health and Science University, Portland, OR, 97239, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Baric, Ralph S" sort="Baric, Ralph S" uniqKey="Baric R" first="Ralph S" last="Baric">Ralph S. Baric</name><affiliation><nlm:affiliation>Department of Epidemiology, University of North Carolina Chapel Hill, Chapel Hill, NC, 27599, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Katze, Michael G" sort="Katze, Michael G" uniqKey="Katze M" first="Michael G" last="Katze">Michael G. Katze</name><affiliation><nlm:affiliation>Department of Microbiology, University of Washington, Seattle, WA, 98195, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Waters, Katrina M" sort="Waters, Katrina M" uniqKey="Waters K" first="Katrina M" last="Waters">Katrina M. Waters</name><affiliation><nlm:affiliation>Computational Biology and Bioinformatics Group, Pacific Northwest National Laboratory, Richland, WA, 99354, USA.</nlm:affiliation></affiliation></author></analytic><series><title level="j">BMC systems biology</title><idno type="eISSN">1752-0509</idno><imprint><date when="2016" type="published">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The complex interplay between viral replication and host immune response during infection remains poorly understood. While many viruses are known to employ anti-immune strategies to facilitate their replication, highly pathogenic virus infections can also cause an excessive immune response that exacerbates, rather than reduces pathogenicity. To investigate this dichotomy in severe acute respiratory syndrome coronavirus (SARS-CoV), we developed a transcriptional network model of SARS-CoV infection in mice and used the model to prioritize candidate regulatory targets for further investigation.</div></front></TEI><pubmed><MedlineCitation Status="PubMed-not-MEDLINE" Owner="NLM"><PMID Version="1">27663205</PMID><DateRevised><Year>2020</Year><Month>04</Month><Day>04</Day></DateRevised><Article PubModel="Electronic"><Journal><ISSN IssnType="Electronic">1752-0509</ISSN><JournalIssue CitedMedium="Internet"><Volume>10</Volume><Issue>1</Issue><PubDate><Year>2016</Year><Month>Sep</Month><Day>23</Day></PubDate></JournalIssue><Title>BMC systems biology</Title><ISOAbbreviation>BMC Syst Biol</ISOAbbreviation></Journal><ArticleTitle>The effect of inhibition of PP1 and TNFα signaling on pathogenesis of SARS coronavirus.</ArticleTitle><Pagination><MedlinePgn>93</MedlinePgn></Pagination><Abstract><AbstractText Label="BACKGROUND" NlmCategory="BACKGROUND">The complex interplay between viral replication and host immune response during infection remains poorly understood. While many viruses are known to employ anti-immune strategies to facilitate their replication, highly pathogenic virus infections can also cause an excessive immune response that exacerbates, rather than reduces pathogenicity. To investigate this dichotomy in severe acute respiratory syndrome coronavirus (SARS-CoV), we developed a transcriptional network model of SARS-CoV infection in mice and used the model to prioritize candidate regulatory targets for further investigation.</AbstractText><AbstractText Label="RESULTS" NlmCategory="RESULTS">We validated our predictions in 18 different knockout (KO) mouse strains, showing that network topology provides significant predictive power to identify genes that are important for viral infection. We identified a novel player in the immune response to virus infection, Kepi, an inhibitory subunit of the protein phosphatase 1 (PP1) complex, which protects against SARS-CoV pathogenesis. We also found that receptors for the proinflammatory cytokine tumor necrosis factor alpha (TNFα) promote pathogenesis, presumably through excessive inflammation.</AbstractText><AbstractText Label="CONCLUSIONS" NlmCategory="CONCLUSIONS">The current study provides validation of network modeling approaches for identifying important players in virus infection pathogenesis, and a step forward in understanding the host response to an important infectious disease. The results presented here suggest the role of Kepi in the host response to SARS-CoV, as well as inflammatory activity driving pathogenesis through TNFα signaling in SARS-CoV infections. Though we have reported the utility of this approach in bacterial and cell culture studies previously, this is the first comprehensive study to confirm that network topology can be used to predict phenotypes in mice with experimental validation.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>McDermott</LastName><ForeName>Jason E</ForeName><Initials>JE</Initials><AffiliationInfo><Affiliation>Computational Biology and Bioinformatics Group, Pacific Northwest National Laboratory, Richland, WA, 99354, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Mitchell</LastName><ForeName>Hugh D</ForeName><Initials>HD</Initials><AffiliationInfo><Affiliation>Computational Biology and Bioinformatics Group, Pacific Northwest National Laboratory, Richland, WA, 99354, USA. Hugh.Mitchell@pnnl.gov.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Gralinski</LastName><ForeName>Lisa E</ForeName><Initials>LE</Initials><AffiliationInfo><Affiliation>Department of Epidemiology, University of North Carolina Chapel Hill, Chapel Hill, NC, 27599, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Eisfeld</LastName><ForeName>Amie J</ForeName><Initials>AJ</Initials><AffiliationInfo><Affiliation>Department of Pathobiological Sciences, School of Veterinary Medicine, Influenza Research Institute, University of Wisconsin-Madison, Madison, WI, 53715, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Josset</LastName><ForeName>Laurence</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>Department of Microbiology, University of Washington, Seattle, WA, 98195, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Bankhead</LastName><ForeName>Armand</ForeName><Initials>A</Initials><Suffix>3rd</Suffix><AffiliationInfo><Affiliation>Division of Biostatistics, Department of Public Health and Preventive Medicine, Oregon Health and Science University, Portland, OR, 97239, USA.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Knight Cancer Institute, Oregon Health and Science University, Portland, OR, 97239, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Neumann</LastName><ForeName>Gabriele</ForeName><Initials>G</Initials><AffiliationInfo><Affiliation>Department of Pathobiological Sciences, School of Veterinary Medicine, Influenza Research Institute, University of Wisconsin-Madison, Madison, WI, 53715, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Tilton</LastName><ForeName>Susan C</ForeName><Initials>SC</Initials><AffiliationInfo><Affiliation>Computational Biology and Bioinformatics Group, Pacific Northwest National Laboratory, Richland, WA, 99354, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Schäfer</LastName><ForeName>Alexandra</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Department of Epidemiology, University of North Carolina Chapel Hill, Chapel Hill, NC, 27599, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Li</LastName><ForeName>Chengjun</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>Department of Pathobiological Sciences, School of Veterinary Medicine, Influenza Research Institute, University of Wisconsin-Madison, Madison, WI, 53715, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Fan</LastName><ForeName>Shufang</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Department of Pathobiological Sciences, School of Veterinary Medicine, Influenza Research Institute, University of Wisconsin-Madison, Madison, WI, 53715, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>McWeeney</LastName><ForeName>Shannon</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Division of Biostatistics, Department of Public Health and Preventive Medicine, Oregon Health and Science University, Portland, OR, 97239, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Baric</LastName><ForeName>Ralph S</ForeName><Initials>RS</Initials><AffiliationInfo><Affiliation>Department of Epidemiology, University of North Carolina Chapel Hill, Chapel Hill, NC, 27599, USA.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Katze</LastName><ForeName>Michael G</ForeName><Initials>MG</Initials><AffiliationInfo><Affiliation>Department of Microbiology, University of Washington, Seattle, WA, 98195, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Waters</LastName><ForeName>Katrina M</ForeName><Initials>KM</Initials><AffiliationInfo><Affiliation>Computational Biology and Bioinformatics Group, Pacific Northwest National Laboratory, Richland, WA, 99354, USA.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><GrantList CompleteYN="Y"><Grant><GrantID>HHSN272200800060C</GrantID><Acronym>AI</Acronym><Agency>NIAID NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>U19 AI106772</GrantID><Acronym>AI</Acronym><Agency>NIAID NIH HHS</Agency><Country>United States</Country></Grant></GrantList><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2016</Year><Month>09</Month><Day>23</Day></ArticleDate></Article><MedlineJournalInfo><Country>England</Country><MedlineTA>BMC Syst Biol</MedlineTA><NlmUniqueID>101301827</NlmUniqueID><ISSNLinking>1752-0509</ISSNLinking></MedlineJournalInfo><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">Network</Keyword><Keyword MajorTopicYN="N">Pathogenicity</Keyword><Keyword MajorTopicYN="N">SARS coronavirus</Keyword><Keyword MajorTopicYN="N">Systems biology</Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2016</Year><Month>01</Month><Day>29</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2016</Year><Month>09</Month><Day>08</Day></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2016</Year><Month>9</Month><Day>25</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2016</Year><Month>9</Month><Day>25</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate 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