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The nonstructural protein 2A protease (2A<jats:sup>pro<\/jats:sup>) of EV, which functions in cleavage of host proteins, comprises an essential part of the viral immune evasion process. However, the pathogenic mechanism of EV-D68 is not fully understood. Here, we show for the first time that EV-D68 inhibited antiviral type I interferon responses by cleaving tumor necrosis factor receptor-associated factor 3 (TRAF3). Furthermore, we identified the key cleavage site in TRAF3. Our study may suggest a new mechanism by which the 2A<jats:sup>pro<\/jats:sup>of EV facilitates subversion of host innate immune responses. These findings increase our understanding of EV-D68 infection and may help identify new antiviral targets against EV-D68.<\/jats:p>","DOI":"10.1128\/jvi.01856-20","type":"journal-article","created":{"date-parts":[[2020,11,2]],"date-time":"2020-11-02T13:50:18Z","timestamp":1604325018000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":32,"title":["Enterovirus D68 Protease 2A<sup>pro<\/sup>Targets TRAF3 To Subvert Host Innate Immune Responses"],"prefix":"10.1128","volume":"95","author":[{"given":"Jun","family":"Kang","sequence":"first","affiliation":[{"name":"School of Life Sciences, Tianjin University, Tianjin, China"},{"name":"Tianjin Key Laboratory of Function and Application of Biological Macromolecular Structures, Tianjin University, Tianjin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3752-5711","authenticated-orcid":false,"given":"Zheng","family":"Pang","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Tianjin University, Tianjin, China"},{"name":"Tianjin International Joint Academy of Biomedicine, Tianjin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenwei","family":"Zhou","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Tianjin University, Tianjin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianhuang","family":"Li","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Tianjin University, Tianjin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sihua","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Tianjin University, Tianjin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinyan","family":"Cheng","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Tianjin University, Tianjin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peiyuan","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Tianjin University, Tianjin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjie","family":"Tan","sequence":"additional","affiliation":[{"name":"National Institute for Viral Disease Control and Prevention, China CDC, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiyun","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Environmental Science and Engineering, Tianjin University, Tianjin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Tianjin University, Tianjin, China"},{"name":"Tianjin Key Laboratory of Function and Application of Biological Macromolecular Structures, Tianjin University, Tianjin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","unstructured":"The Pirbright Institute. 2013. 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