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dc.contributor.authorKulcsar, K.A.
dc.contributor.authorColeman, C.M.
dc.contributor.authorFrieman, M.B.
dc.date.accessioned2020-02-04T16:19:39Z
dc.date.available2020-02-04T16:19:39Z
dc.date.issued2019
dc.identifier.urihttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85078200507&doi=10.1172%2fjci.insight.131774&partnerID=40&md5=6eced8584f9327d7268581f82c9534d8
dc.identifier.urihttp://hdl.handle.net/10713/11665
dc.description.abstractMiddle East respiratory syndrome coronavirus (MERS-CoV) emerged in 2012 in Saudi Arabia and has caused over 2400 cases and more than 800 deaths. Epidemiological studies identified diabetes as the primary comorbidity associated with severe or lethal MERS-CoV infection. Understanding how diabetes affects MERS is important because of the global burden of diabetes and pandemic potential of MERS-CoV. We used a model in which mice were made susceptible to MERS-CoV by expressing human DPP4, and type 2 diabetes was induced by administering a high-fat diet. Upon infection with MERS-CoV, diabetic mice had a prolonged phase of severe disease and delayed recovery that was independent of virus titers. Histological analysis revealed that diabetic mice had delayed inflammation, which was then prolonged through 21 days after infection. Diabetic mice had fewer inflammatory monocyte/macrophages and CD4+ T cells, which correlated with lower levels of Ccl2 and Cxcl10 expression. Diabetic mice also had lower levels of Tnfa, Il6, Il12b, and Arg1 expression and higher levels of Il17a expression. These data suggest that the increased disease severity observed in individuals with MERS and comorbid type 2 diabetes is likely due to a dysregulated immune response, which results in more severe and prolonged lung pathology.en_US
dc.description.sponsorshipThis study was supported by NIH/National Institute of Allergy and Infectious Diseases R21-AI126300, T32-AI095190, F32-AI136390 and K01-OD021323.en_US
dc.description.urihttps://doi.org/10.1172/jci.insight.131774en_US
dc.language.isoen_USen_US
dc.publisherAmerican Society for Clinical Investigationen_US
dc.relation.ispartofJCI Insight
dc.subject.meshComorbidityen_US
dc.subject.meshMiddle East Respiratory Syndrome Coronavirusen_US
dc.subject.meshDiabetes Mellitus, Type 2en_US
dc.titleComorbid diabetes results in immune dysregulation and enhanced disease severity following MERS-CoV infectionen_US
dc.typeArticleen_US
dc.identifier.doi10.1172/jci.insight.131774
dc.identifier.pmid31550243


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