AUTHOR=Wang Yin , Abe Jun-ichi , Chau Khanh M. , Wang Yongxing , Vu Hang Thi , Reddy Velatooru Loka , Gulraiz Fahad , Imanishi Masaki , Samanthapudi Venkata S. K. , Nguyen Minh T. H. , Ko Kyung Ae , Lee Ling-Ling , Thomas Tamlyn N. , Olmsted-Davis Elizabeth A. , Kotla Sivareddy , Fujiwara Keigi , Cooke John P. , Zhao Di , Evans Scott E. , Le Nhat-Tu TITLE=MAGI1 inhibits interferon signaling to promote influenza A infection JOURNAL=Frontiers in Cardiovascular Medicine VOLUME=9 YEAR=2022 URL=https://www.frontiersin.org/journals/cardiovascular-medicine/articles/10.3389/fcvm.2022.791143 DOI=10.3389/fcvm.2022.791143 ISSN=2297-055X ABSTRACT=
We have shown that membrane-associated guanylate kinase with inverted domain structure-1 (MAGI1), a scaffold protein with six PSD95/DiscLarge/ZO-1 (PDZ) domains, is involved in the regulation of endothelial cell (EC) activation and atherogenesis in mice. In addition to causing acute respiratory disease, influenza A virus (IAV) infection plays an important role in atherogenesis and triggers acute coronary syndromes and fatal myocardial infarction. Therefore, the aim of this study is to investigate the function and regulation of MAGI1 in IAV-induced EC activation. Whereas, EC infection by IAV increases MAGI1 expression, MAGI1 depletion suppresses IAV infection, suggesting that the induction of MAGI1 may promote IAV infection. Treatment of ECs with oxidized low-density lipoprotein (OxLDL) increases MAGI1 expression and IAV infection, suggesting that MAGI1 is part of the mechanistic link between serum lipid levels and patient prognosis following IAV infection. Our microarray studies suggest that MAGI1-depleted ECs increase protein expression and signaling networks involve in interferon (IFN) production. Specifically, infection of MAGI1-null ECs with IAV upregulates expression of signal transducer and activator of transcription 1 (STAT1), interferon b1 (IFNb1), myxovirus resistance protein 1 (MX1) and 2′-5′-oligoadenylate synthetase 2 (OAS2), and activate STAT5. By contrast, MAGI1 overexpression inhibits