nad a22 4500 569231310 20190724072231.0 cr unu---uuuuu 190724e20140501xx s 000 0 eng 10.5167/uzh-172000 doi 10.1007/s00395-014-0411-3 doi (ZORA)oai:www.zora.uzh.ch:172000 610 ddc The adapter protein c-Cbl-associated protein (CAP) protects from acute CVB3-mediated myocarditis through stabilization of type I interferon production and reduced cytotoxicity [Elektronische Daten] [Alan Valaperti, Mototsugu Nishii, Youan Liu, Howard Yang, Kotaro Naito, Peter P Liu, Urs Eriksson] openAccess eu-repo c-Cbl-associated protein (CAP), also called Sorbs1 or ponsin, has been described as an essential adapter protein in the insulin-signalling pathway. Here, we describe for the first time a unique protective role for CAP in viral myocarditis. Mortality and heart failure development were increased in CAP−/− mice compared to CAP+/+ littermates after Coxsackievirus (CVB3) infection. Mechanistically, CAP protected from tissue apoptosis because of reduced CD8+ T and natural killer cell cytotoxicity. Despite reduced cytotoxic elimination of CVB3-infected cells in CAP+/+ hearts, however, CAP enhanced interferon regulatory factor 3(IRF3)-dependent antiviral type I interferon production and decreased viral proliferation in vitro by binding to the cytoplasmic RIG-I-like receptor melanoma differentiation-associated protein 5 (MDA5). Taken together, these findings reveal a novel modulatory role for CAP in the heart as a key protein stabilizing antiviral type I interferon production, while protecting from excessive cytotoxic responses. Our study will help to define future strategies to develop treatments to limit detrimental responses during viral heart inflammation. 142-005 zora Physiology (medical), Physiology, Cardiology and Cardiovascular Medicine zora Valaperti Alan joint author Nishii Mototsugu joint author Liu Youan joint author Yang Howard joint author Naito Kotaro joint author Liu Peter P. joint author Eriksson Urs joint author Basic Research in Cardiology 109(3):411 https://www.zora.uzh.ch/id/eprint/172000/1/ZORA_NL_172000.pdf text/html WWW-Backlink auf das Repository 1 Journal Article PeerReviewed zora ZORA 856 40 https://www.zora.uzh.ch/id/eprint/172000/1/ZORA_NL_172000.pdf text/html WWW-Backlink auf das Repository ZORA 700 1- Valaperti Alan joint author ZORA 700 1- Nishii Mototsugu joint author ZORA 700 1- Liu Youan joint author ZORA 700 1- Yang Howard joint author ZORA 700 1- Naito Kotaro joint author ZORA 700 1- Liu Peter P. joint author ZORA 700 1- Eriksson Urs joint author ZORA 773 0- Basic Research in Cardiology 109(3):411 SWISSBIB 560893620 BK010053 XK010053 XK010000 ZORA ZORA ZORA Journal Article openAccess