{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T09:49:35Z","timestamp":1793180975671,"version":"4.5.0"},"reference-count":46,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2020,4,9]],"date-time":"2020-04-09T00:00:00Z","timestamp":1586390400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"Research Center for Emerging Viral Infections"},{"name":"The Featured Areas Research Center Program"},{"name":"Higher Education Sprout Project by the Ministry of Education"},{"DOI":"10.13039\/501100003711","name":"Ministry of Science and Technology","doi-asserted-by":"publisher","award":["MOST 107-3017-F-182-001"],"award-info":[{"award-number":["MOST 107-3017-F-182-001"]}],"id":[{"id":"10.13039\/501100003711","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology, Taiwan","doi-asserted-by":"publisher","award":["MOST-107-2320-B-182-008"],"award-info":[{"award-number":["MOST-107-2320-B-182-008"]}],"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":["MOST108-2320-B-182-033"],"award-info":[{"award-number":["MOST108-2320-B-182-033"]}],"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":["MOST106-2362-B-182-001"],"award-info":[{"award-number":["MOST106-2362-B-182-001"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012553","name":"Chang Gung Memorial Hospital","doi-asserted-by":"publisher","award":["CMRPD1G0431"],"award-info":[{"award-number":["CMRPD1G0431"]}],"id":[{"id":"10.13039\/100012553","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012553","name":"Chang Gung Memorial Hospital","doi-asserted-by":"publisher","award":["BMRPB33"],"award-info":[{"award-number":["BMRPB33"]}],"id":[{"id":"10.13039\/100012553","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,7,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Enterovirus A71 (EV-A71) has been noted for its tendency to lead to neurological manifestations in young children and infants. Although the alimentary tract has been identified as the primary replication site of this virus, how EV-A71 replicates in the gut and is transmitted to other organs remains unclear.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>By using differentiated C2BBe1 cells as a model, we observed that intestinal epithelial cells (IECs) were permissive to EV-A71 infection, and viral particles were released in a nonlytic manner.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>The coexistence of active caspase 3 and EV-A71 protein was observed in the infected undifferentiated C2BBe1 and RD cells but not in the infected differentiated C2BBe1 cells. Furthermore, EV-A71 infection caused differentiated C2BBe1 and intestinal organoids to secrete exosomes containing viral components and have the ability to establish active infection. Inhibition of the exosome pathway decreased EV-A71 replication and release in IECs and increased the survival rates of infected animals.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Our findings showed that EV-A71 is able to be actively replicated in enterocytes, and that the exosome pathway is involved in the nonlytic release of viral particles, which may be useful for developing antiviral strategies.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/infdis\/jiaa174","type":"journal-article","created":{"date-parts":[[2020,4,7]],"date-time":"2020-04-07T21:42:42Z","timestamp":1586295762000},"page":"456-469","source":"Crossref","is-referenced-by-count":42,"title":["Exosomes Facilitate Transmission of Enterovirus A71 From Human Intestinal Epithelial Cells"],"prefix":"10.1093","volume":"222","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4348-7851","authenticated-orcid":false,"given":"Hsing-I","family":"Huang","sequence":"first","affiliation":[{"name":"Department of Medical Biotechnology and Laboratory Science, College of Medicine, Chang Gung University, Kwei-Shan, Tao-Yuan, Taiwan"},{"name":"Research Center for Emerging Viral Infections, College of Medicine, Chang Gung University, Kwei-Shan, Tao-Yuan, Taiwan"},{"name":"Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Kwei-Shan, Tao-Yuan, Taiwan"},{"name":"Department of Pediatrics, Linkou Chang Gung Memorial Hospital, Kwei-Shan, Tao-Yuan, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jhao-Yin","family":"Lin","sequence":"first","affiliation":[{"name":"Department of Medical Biotechnology and Laboratory Science, College of Medicine, Chang Gung University, Kwei-Shan, Tao-Yuan, Taiwan"},{"name":"Research Center for Emerging Viral Infections, College of Medicine, Chang Gung University, Kwei-Shan, Tao-Yuan, Taiwan"},{"name":"Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Kwei-Shan, Tao-Yuan, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hsiao-Chu","family":"Chiang","sequence":"first","affiliation":[{"name":"Department of Medical Biotechnology and Laboratory Science, College of Medicine, Chang Gung University, Kwei-Shan, Tao-Yuan, Taiwan"},{"name":"Research Center for Emerging Viral Infections, College of Medicine, Chang Gung University, Kwei-Shan, Tao-Yuan, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pen-Nien","family":"Huang","sequence":"first","affiliation":[{"name":"Research Center for Emerging Viral Infections, College of Medicine, Chang Gung University, Kwei-Shan, Tao-Yuan, Taiwan"},{"name":"Department of Pediatrics, Linkou Chang Gung Memorial Hospital, Kwei-Shan, Tao-Yuan, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing-Dong","family":"Lin","sequence":"first","affiliation":[{"name":"Institute of Systems Biology and Bioinformatics, National Central University, Taoyuan City, Taiwan"},{"name":"Cathay Medical Research Institute, Cathay General Hospital, New Taipei City, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shin-Ru","family":"Shih","sequence":"first","affiliation":[{"name":"Department of Medical Biotechnology and Laboratory Science, College of Medicine, Chang Gung University, Kwei-Shan, Tao-Yuan, Taiwan"},{"name":"Research Center for Emerging Viral Infections, College of Medicine, Chang Gung University, Kwei-Shan, Tao-Yuan, Taiwan"},{"name":"Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Kwei-Shan, Tao-Yuan, Taiwan"},{"name":"Department of Laboratory Medicine, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan"},{"name":"Research Center for Chinese Herbal Medicine, Research Center for Food and Cosmetic Safety, and Graduate Institute of Health Industry Technology, College of Human Ecology, Chang Gung University of Science and Technology, Taoyuan, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,4,9]]},"reference":[{"key":"2020070607240967900_CIT0001","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1056\/NEJM199909233411301","article-title":"An epidemic of enterovirus 71 infection in Taiwan. 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