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    Comorbid diabetes results in immune dysregulation and enhanced disease severity following MERS-CoV infection

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    Author
    Kulcsar, K.A.
    Coleman, C.M.
    Frieman, M.B.
    Date
    2019
    Journal
    JCI Insight
    Publisher
    American Society for Clinical Investigation
    Type
    Article
    
    Metadata
    Show full item record
    See at
    https://doi.org/10.1172/jci.insight.131774
    Abstract
    Middle 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.
    Sponsors
    This study was supported by NIH/National Institute of Allergy and Infectious Diseases R21-AI126300, T32-AI095190, F32-AI136390 and K01-OD021323.
    Keyword
    Comorbidity
    Middle East Respiratory Syndrome Coronavirus
    Diabetes Mellitus, Type 2
    Identifier to cite or link to this item
    https://www.scopus.com/inward/record.uri?eid=2-s2.0-85078200507&doi=10.1172%2fjci.insight.131774&partnerID=40&md5=6eced8584f9327d7268581f82c9534d8; http://hdl.handle.net/10713/11665
    ae974a485f413a2113503eed53cd6c53
    10.1172/jci.insight.131774
    Scopus Count
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