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<PubmedArticle><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">27096319</PMID><DateCompleted><Year>2016</Year><Month>09</Month><Day>26</Day></DateCompleted><DateRevised><Year>2021</Year><Month>01</Month><Day>08</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Electronic">1097-4180</ISSN><JournalIssue CitedMedium="Internet"><Volume>44</Volume><Issue>4</Issue><PubDate><Year>2016</Year><Month>Apr</Month><Day>19</Day></PubDate></JournalIssue><Title>Immunity</Title><ISOAbbreviation>Immunity</ISOAbbreviation></Journal><ArticleTitle>Brain Endothelial- and Epithelial-Specific Interferon Receptor Chain 1 Drives Virus-Induced Sickness Behavior and Cognitive Impairment.</ArticleTitle><Pagination><StartPage>901</StartPage><EndPage>912</EndPage><MedlinePgn>901-12</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1016/j.immuni.2016.04.005</ELocationID><ELocationID EIdType="pii" ValidYN="Y">S1074-7613(16)30110-8</ELocationID><Abstract><AbstractText>Sickness behavior and cognitive dysfunction occur frequently by unknown mechanisms in virus-infected individuals with malignancies treated with type I interferons (IFNs) and in patients with autoimmune disorders. We found that during sickness behavior, single-stranded RNA viruses, double-stranded RNA ligands, and IFNs shared pathways involving engagement of melanoma differentiation-associated protein 5 (MDA5), retinoic acid-inducible gene 1 (RIG-I), and mitochondrial antiviral signaling protein (MAVS), and subsequently induced IFN responses specifically in brain endothelia and epithelia of mice. Behavioral alterations were specifically dependent on brain endothelial and epithelial IFN receptor chain 1 (IFNAR). Using gene profiling, we identified that the endothelia-derived chemokine ligand CXCL10 mediated behavioral changes through impairment of synaptic plasticity. These results identified brain endothelial and epithelial cells as natural gatekeepers for virus-induced sickness behavior, demonstrated tissue specific IFNAR engagement, and established the CXCL10-CXCR3 axis as target for the treatment of behavioral changes during virus infection and type I IFN therapy.</AbstractText><CopyrightInformation>Copyright &#xa9; 2016 Elsevier Inc. All rights reserved.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Blank</LastName><ForeName>Thomas</ForeName><Initials>T</Initials><AffiliationInfo><Affiliation>Institute of Neuropathology, University of Freiburg, 79106 Freiburg, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Detje</LastName><ForeName>Claudia N</ForeName><Initials>CN</Initials><AffiliationInfo><Affiliation>Institute for Experimental Infection Research, TWINCORE, Centre for Experimental and Clinical Infection Research, a joint venture between the Helmholtz Centre for Infection Research and the Medical School Hannover, 30625 Hannover, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Spie&#xdf;</LastName><ForeName>Alena</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Institute of Neuropathology, University of Freiburg, 79106 Freiburg, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Hagemeyer</LastName><ForeName>Nora</ForeName><Initials>N</Initials><AffiliationInfo><Affiliation>Institute of Neuropathology, University of Freiburg, 79106 Freiburg, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Brendecke</LastName><ForeName>Stefanie M</ForeName><Initials>SM</Initials><AffiliationInfo><Affiliation>Institute of Neuropathology, University of Freiburg, 79106 Freiburg, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Wolfart</LastName><ForeName>Jakob</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Oscar Langendorff Institute of Physiology, University of Rostock, 18057 Rostock, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Staszewski</LastName><ForeName>Ori</ForeName><Initials>O</Initials><AffiliationInfo><Affiliation>Institute of Neuropathology, University of Freiburg, 79106 Freiburg, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Z&#xf6;ller</LastName><ForeName>Tanja</ForeName><Initials>T</Initials><AffiliationInfo><Affiliation>Institute of Neuropathology, University of Freiburg, 79106 Freiburg, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Papageorgiou</LastName><ForeName>Ismini</ForeName><Initials>I</Initials><AffiliationInfo><Affiliation>Institute of Physiology and Pathophysiology, University of Heidelberg, 69120 Heidelberg, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Schneider</LastName><ForeName>Justus</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Institute of Physiology and Pathophysiology, University of Heidelberg, 69120 Heidelberg, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Paricio-Montesinos</LastName><ForeName>Ricardo</ForeName><Initials>R</Initials><AffiliationInfo><Affiliation>Institute of Neuropathology, University of Freiburg, 79106 Freiburg, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Eisel</LastName><ForeName>Ulrich L M</ForeName><Initials>UL</Initials><AffiliationInfo><Affiliation>Department of Molecular Neurobiology, Groningen Institute of Evolutionary Life Sciences, University of Groningen, and Department of Psychiatry, University Medical Center Groningen, 9700 Groningen, The Netherlands.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Manahan-Vaughan</LastName><ForeName>Denise</ForeName><Initials>D</Initials><AffiliationInfo><Affiliation>Ruhr University Bochum, Medical Faculty, Department Neurophysiology, 44780 Bochum, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Jansen</LastName><ForeName>Stephan</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Ruhr University Bochum, Medical Faculty, Department Neurophysiology, 44780 Bochum, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Lienenklaus</LastName><ForeName>Stefan</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Institute for Experimental Infection Research, TWINCORE, Centre for Experimental and Clinical Infection Research, a joint venture between the Helmholtz Centre for Infection Research and the Medical School Hannover, 30625 Hannover, Germany; Institute for Laboratory Animal Science, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625 Hannover, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Lu</LastName><ForeName>Bao</ForeName><Initials>B</Initials><AffiliationInfo><Affiliation>Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Imai</LastName><ForeName>Yumiko</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>Department of Biological Informatics and Experimental Therapeutics, Akita University Graduate School of Medicine, Akita 010-8543, Japan.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>M&#xfc;ller</LastName><ForeName>Marcus</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Department of Neurology, Universit&#xe4;tsklinikum Bonn, 53105 Bonn, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Goelz</LastName><ForeName>Susan E</ForeName><Initials>SE</Initials><AffiliationInfo><Affiliation>Portland, Oregon, 97201, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Baker</LastName><ForeName>Darren P</ForeName><Initials>DP</Initials><AffiliationInfo><Affiliation>Biogen Inc., Cambridge, MA 02142, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Schwaninger</LastName><ForeName>Markus</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Institute of Experimental and Clinical Pharmacology and Toxicology, University of L&#xfc;beck, 23538 L&#xfc;beck, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Kann</LastName><ForeName>Oliver</ForeName><Initials>O</Initials><AffiliationInfo><Affiliation>Institute of Physiology and Pathophysiology, University of Heidelberg, 69120 Heidelberg, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Heikenwalder</LastName><ForeName>Mathias</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Institute of Virology, Technische Universit&#xe4;t M&#xfc;nchen/ Helmholtz-Zentrum M&#xfc;nchen, 81756 M&#xfc;nchen, Germany; Division of Chronic Inflammation and Cancer, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Kalinke</LastName><ForeName>Ulrich</ForeName><Initials>U</Initials><AffiliationInfo><Affiliation>Institute for Experimental Infection Research, TWINCORE, Centre for Experimental and Clinical Infection Research, a joint venture between the Helmholtz Centre for Infection Research and the Medical School Hannover, 30625 Hannover, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Prinz</LastName><ForeName>Marco</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Institute of Neuropathology, University of Freiburg, 79106 Freiburg, Germany; BIOSS Centre for Biological Signalling Studies, University of Freiburg, 79104 Freiburg, Germany. Electronic address: marco.prinz@uniklinik-freiburg.de.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><DataBankList CompleteYN="Y"><DataBank><DataBankName>GEO</DataBankName><AccessionNumberList><AccessionNumber>GSE74063</AccessionNumber></AccessionNumberList></DataBank></DataBankList><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Immunity</MedlineTA><NlmUniqueID>9432918</NlmUniqueID><ISSNLinking>1074-7613</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D048868">Adaptor Proteins, Signal Transducing</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D054357">Chemokine CXCL10</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C485433">Cxcl10 protein, mouse</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C515188">Cxcr3 protein, mouse</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C512612">IPS-1 protein, mouse</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C508032">Ifnar1 protein, mouse</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D007370">Interferon Type I</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D012330">RNA, Double-Stranded</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D054367">Receptors, CXCR3</NameOfSubstance></Chemical><Chemical><RegistryNumber>156986-95-7</RegistryNumber><NameOfSubstance UI="D053633">Receptor, Interferon alpha-beta</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 3.6.1.-</RegistryNumber><NameOfSubstance UI="C503356">Ddx58 protein, mouse</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 3.6.1.-</RegistryNumber><NameOfSubstance UI="C510592">Ifih1 protein, mouse</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 3.6.4.13</RegistryNumber><NameOfSubstance UI="D000071457">DEAD Box Protein 58</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 3.6.4.13</RegistryNumber><NameOfSubstance UI="D053487">DEAD-box RNA Helicases</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 3.6.4.13</RegistryNumber><NameOfSubstance UI="D000072640">Interferon-Induced Helicase, IFIH1</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><CommentsCorrectionsList><CommentsCorrections RefType="CommentIn"><RefSource>Immunity. 2016 Apr 19;44(4):718-20. doi: 10.1016/j.immuni.2016.03.010</RefSource><PMID Version="1">27096312</PMID></CommentsCorrections></CommentsCorrectionsList><MeshHeadingList><MeshHeading><DescriptorName UI="D048868" MajorTopicYN="N">Adaptor Proteins, Signal Transducing</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D001921" MajorTopicYN="N">Brain</DescriptorName><QualifierName UI="Q000166" MajorTopicYN="Y">cytology</QualifierName><QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D002450" MajorTopicYN="N">Cell Communication</DescriptorName><QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D002478" MajorTopicYN="N">Cells, Cultured</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D054357" MajorTopicYN="N">Chemokine CXCL10</DescriptorName><QualifierName UI="Q000276" MajorTopicYN="Y">immunology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D003072" MajorTopicYN="N">Cognition Disorders</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName><QualifierName UI="Q000523" MajorTopicYN="N">psychology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D000071457" MajorTopicYN="N">DEAD Box Protein 58</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D053487" MajorTopicYN="N">DEAD-box RNA Helicases</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D042783" MajorTopicYN="N">Endothelial Cells</DescriptorName><QualifierName UI="Q000276" MajorTopicYN="Y">immunology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D004727" MajorTopicYN="N">Endothelium</DescriptorName><QualifierName UI="Q000166" MajorTopicYN="N">cytology</QualifierName><QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D004847" MajorTopicYN="N">Epithelial Cells</DescriptorName><QualifierName UI="Q000276" MajorTopicYN="Y">immunology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D004848" MajorTopicYN="N">Epithelium</DescriptorName><QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D055809" MajorTopicYN="N">Illness Behavior</DescriptorName><QualifierName UI="Q000502" MajorTopicYN="Y">physiology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D007370" MajorTopicYN="N">Interferon Type I</DescriptorName><QualifierName UI="Q000627" MajorTopicYN="N">therapeutic use</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D000072640" MajorTopicYN="N">Interferon-Induced Helicase, IFIH1</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008297" MajorTopicYN="N">Male</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D051379" MajorTopicYN="N">Mice</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D012330" MajorTopicYN="N">RNA, Double-Stranded</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D053633" MajorTopicYN="N">Receptor, Interferon alpha-beta</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName><QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D054367" MajorTopicYN="N">Receptors, CXCR3</DescriptorName><QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D015398" MajorTopicYN="N">Signal Transduction</DescriptorName><QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D014777" MajorTopicYN="N">Virus Diseases</DescriptorName><QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName></MeshHeading></MeshHeadingList><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">CXCL10</Keyword><Keyword MajorTopicYN="N">CXCR3</Keyword><Keyword MajorTopicYN="N">IFN</Keyword><Keyword MajorTopicYN="N">IFNAR1</Keyword><Keyword MajorTopicYN="N">IPS-1</Keyword><Keyword MajorTopicYN="N">MAVS</Keyword><Keyword MajorTopicYN="N">behavior</Keyword><Keyword MajorTopicYN="N">brain</Keyword><Keyword MajorTopicYN="N">depression</Keyword><Keyword MajorTopicYN="N">endothelia</Keyword><Keyword MajorTopicYN="N">epithelia</Keyword><Keyword MajorTopicYN="N">influenza</Keyword><Keyword MajorTopicYN="N">neurons</Keyword><Keyword MajorTopicYN="N">signal transduction</Keyword><Keyword MajorTopicYN="N">type I interferon</Keyword><Keyword MajorTopicYN="N">virus infection</Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2014</Year><Month>11</Month><Day>3</Day></PubMedPubDate><PubMedPubDate PubStatus="revised"><Year>2015</Year><Month>10</Month><Day>19</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2016</Year><Month>1</Month><Day>5</Day></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2016</Year><Month>4</Month><Day>21</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2016</Year><Month>4</Month><Day>21</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2016</Year><Month>9</Month><Day>27</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">27096319</ArticleId><ArticleId IdType="doi">10.1016/j.immuni.2016.04.005</ArticleId><ArticleId IdType="pii">S1074-7613(16)30110-8</ArticleId></ArticleIdList></PubmedData></PubmedArticle></PubmedArticleSet>trying2...<BR>trying...<BR>trying2...<BR>

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               <h2><a href="https://www.litmetric.com/detail/27096319/Brain-Endothelial-and-Epithelial-Specific-Interferon-Receptor-Chain-1-Drives-Virus-Induced-Sickness-" >Brain Endothelial- and Epithelial-Specific Interferon Receptor Chain 1 Drives Virus-Induced Sickness Behavior and Cognitive Impairment.</a></h2>
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                <div class="publication-auther"><a href="https://www.litmetric.com/author/Thomas+Blank" class="tag" style="margin-bottom: 5px;">Thomas Blank</a> <a href="https://www.litmetric.com/author/Claudia+N+Detje" class="tag" style="margin-bottom: 5px;">Claudia N Detje</a> <a href="https://www.litmetric.com/author/Alena+SpieSS" class="tag" style="margin-bottom: 5px;">Alena Spieß</a> <a href="https://www.litmetric.com/author/Nora+Hagemeyer" class="tag" style="margin-bottom: 5px;">Nora Hagemeyer</a> <a href="https://www.litmetric.com/author/Stefanie+M+Brendecke" class="tag" style="margin-bottom: 5px;">Stefanie M Brendecke</a> <a href="https://www.litmetric.com/author/Jakob+Wolfart" class="tag" style="margin-bottom: 5px;">Jakob Wolfart</a> <a href="https://www.litmetric.com/author/Ori+Staszewski" class="tag" style="margin-bottom: 5px;">Ori Staszewski</a> <a href="https://www.litmetric.com/author/Tanja+Zoeller" class="tag" style="margin-bottom: 5px;">Tanja Zöller</a> <a href="https://www.litmetric.com/author/Ismini+Papageorgiou" class="tag" style="margin-bottom: 5px;">Ismini Papageorgiou</a> <a href="https://www.litmetric.com/author/Justus+Schneider" class="tag" style="margin-bottom: 5px;">Justus Schneider</a> <a href="https://www.litmetric.com/author/Ricardo+Paricio-Montesinos" class="tag" style="margin-bottom: 5px;">Ricardo Paricio-Montesinos</a> <a href="https://www.litmetric.com/author/Ulrich+L+M+Eisel" class="tag" style="margin-bottom: 5px;">Ulrich L M Eisel</a> <a href="https://www.litmetric.com/author/Denise+Manahan-Vaughan" class="tag" style="margin-bottom: 5px;">Denise Manahan-Vaughan</a> <a href="https://www.litmetric.com/author/Stephan+Jansen" class="tag" style="margin-bottom: 5px;">Stephan Jansen</a> <a href="https://www.litmetric.com/author/Stefan+Lienenklaus" class="tag" style="margin-bottom: 5px;">Stefan Lienenklaus</a> <a href="https://www.litmetric.com/author/Bao+Lu" class="tag" style="margin-bottom: 5px;">Bao Lu</a> <a href="https://www.litmetric.com/author/Yumiko+Imai" class="tag" style="margin-bottom: 5px;">Yumiko Imai</a> <a href="https://www.litmetric.com/author/Marcus+Mueller" class="tag" style="margin-bottom: 5px;">Marcus Müller</a> <a href="https://www.litmetric.com/author/Susan+E+Goelz" class="tag" style="margin-bottom: 5px;">Susan E Goelz</a> <a href="https://www.litmetric.com/author/Darren+P+Baker" class="tag" style="margin-bottom: 5px;">Darren P Baker</a></div>                   
                    <p class="mb-0 dark-color fz15 fw500 list-inline-item ml15 mb5-sm ml0-xs"><i class="flaticon-contract vam fz20 me-2"></i> Immunity</p>
              
                   <p class="mb-0 dark-color fz15 fw500 list-inline-item mr15  mb5-sm ml0-xs"><i class="flaticon-place text-thm2 vam fz20 me-2"></i> Institute of Neuropathology, <a href='https://www.litmetric.com/search/University+of+Freiburg%5BAffiliation%5D' style='text-decoration: underline'>University of Freiburg</a>, 79106 Freiburg, Germany; BIOSS Centre for Biological Signalling Studies, <a href='https://www.litmetric.com/search/University+of+Freiburg%5BAffiliation%5D' style='text-decoration: underline'>University of Freiburg</a>, 79104 Freiburg, Germany. Electronic address: </p>
                    
                     
                   <p class="mb-0 dark-color fz15 fw500 list-inline-item ml15 mb5-sm ml0-xs"><i class="flaticon-calendar vam fz20 me-2"></i> Published: April 2016</p>
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                   <p class="text mb30"><p class="text mt10">Sickness behavior and cognitive dysfunction occur frequently by unknown mechanisms in virus-infected individuals with malignancies treated with type I interferons (IFNs) and in patients with autoimmune disorders. We found that during sickness behavior, single-stranded RNA viruses, double-stranded RNA ligands, and IFNs shared pathways involving engagement of melanoma differentiation-associated protein 5 (MDA5), retinoic acid-inducible gene 1 (RIG-I), and mitochondrial antiviral signaling protein (MAVS), and subsequently induced IFN responses specifically in brain endothelia and epithelia of mice. Behavioral alterations were specifically dependent on brain endothelial and epithelial IFN receptor chain 1 (IFNAR). Using gene profiling, we identified that the endothelia-derived chemokine ligand CXCL10 mediated behavioral changes through impairment of synaptic plasticity. These results identified brain endothelial and epithelial cells as natural gatekeepers for virus-induced sickness behavior, demonstrated tissue specific IFNAR engagement, and established the CXCL10-CXCR3 axis as target for the treatment of behavioral changes during virus infection and type I IFN therapy.</p><table class="table table-bordered table-striped downloadTable" >
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