{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T04:29:34Z","timestamp":1790828974888,"version":"4.1.0"},"reference-count":74,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2018,12,5]],"date-time":"2018-12-05T00:00:00Z","timestamp":1543968000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology, Taiwan","doi-asserted-by":"publisher","award":["NSC-104-2320-B-006-022-MY3"],"award-info":[{"award-number":["NSC-104-2320-B-006-022-MY3"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology, Taiwan","doi-asserted-by":"publisher","award":["NSC-100-2320-B-006-013-MY3"],"award-info":[{"award-number":["NSC-100-2320-B-006-013-MY3"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology, Taiwan","doi-asserted-by":"publisher","award":["106-2918-I-006 -007"],"award-info":[{"award-number":["106-2918-I-006 -007"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006578","name":"Chi Mei Medical Center","doi-asserted-by":"publisher","award":["CMNCKU10424"],"award-info":[{"award-number":["CMNCKU10424"]}],"id":[{"id":"10.13039\/501100006578","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006578","name":"Chi Mei Medical Center","doi-asserted-by":"publisher","award":["CMNCKU10518"],"award-info":[{"award-number":["CMNCKU10518"]}],"id":[{"id":"10.13039\/501100006578","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Enterovirus A71 (EV-A71) has emerged as a major pathogen causing hand, foot, and mouth disease, as well as neurological disorders. The host immune response affects the outcomes of EV-A71 infection, leading to either resolution or disease progression. However, the mechanisms of how the mammalian innate immune system detects EV-A71 infection to elicit antiviral immunity remain elusive. Here, we report that the Toll-like receptor 3 (TLR3) is a key viral RNA sensor for sensing EV-A71 infection to trigger antiviral immunity. Expression of TLR3 in HEK293 cells enabled the cells to sense EV-A71 infection, leading to type I, IFN-mediated antiviral immunity. Viral double-stranded RNA derived from EV-A71 infection was a key ligand for TLR3 detection. Silencing of TLR3 in mouse and human primary immune cells impaired the activation of IFN-\u03b2 upon EV-A71 infection, thus reinforcing the importance of the TLR3 pathway in defending against EV-A71 infection. Our results further demonstrated that TLR3 was a target of EV-A71 infection. EV-A71 protease 2A was implicated in the downregulation of TLR3. Together, our results not only demonstrate the importance of the TLR3 pathway in response to EV-A71 infection, but also reveal the involvement of EV-A71 protease 2A in subverting TLR3-mediated antiviral defenses.<\/jats:p>","DOI":"10.3390\/v10120689","type":"journal-article","created":{"date-parts":[[2018,12,5]],"date-time":"2018-12-05T12:22:00Z","timestamp":1544012520000},"page":"689","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Toll-Like Receptor 3 Is Involved in Detection of Enterovirus A71 Infection and Targeted by Viral 2A Protease"],"prefix":"10.3390","volume":"10","author":[{"given":"Kuan-Ru","family":"Chen","sequence":"first","affiliation":[{"name":"Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan"},{"name":"Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun-Keung","family":"Yu","sequence":"additional","affiliation":[{"name":"Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan"},{"name":"Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan"},{"name":"Center of Infectious Disease and Signaling Research, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Szu-Hao","family":"Kung","sequence":"additional","affiliation":[{"name":"Department of Biotechnology and Laboratory Science in Medicine, National Yang Ming University, Taipei 11221, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shun-Hua","family":"Chen","sequence":"additional","affiliation":[{"name":"Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan"},{"name":"Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan"},{"name":"Center of Infectious Disease and Signaling Research, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuan-Fa","family":"Chang","sequence":"additional","affiliation":[{"name":"Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan"},{"name":"Center of Infectious Disease and Signaling Research, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan"},{"name":"Department of Medical Laboratory Science and Biotechnology, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tzu-Chuan","family":"Ho","sequence":"additional","affiliation":[{"name":"Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-Ping","family":"Lee","sequence":"additional","affiliation":[{"name":"Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan"},{"name":"Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan"},{"name":"Center of Infectious Disease and Signaling Research, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hung-Chuan","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lan-Yin","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Medicine, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shih-Yen","family":"Lo","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Biotechnology, Tzu Chi University, Hualien 97004, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jui-Chung","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Prosthetic Dentistry, Chi-Mei Medical Center, Tainan 71004, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pin","family":"Ling","sequence":"additional","affiliation":[{"name":"Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan"},{"name":"Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan"},{"name":"Center of Infectious Disease and Signaling Research, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan"},{"name":"Department of Medical Laboratory Science and Biotechnology, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,12,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1007\/s11908-012-0267-3","article-title":"The Pathogenesis and Prevention of Encephalitis due to Human Enterovirus 71","volume":"14","author":"Bek","year":"2012","journal-title":"Curr. 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