{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T00:10:16Z","timestamp":1788999016048,"version":"build-2803163510"},"reference-count":74,"publisher":"American Society for Microbiology","issue":"15","license":[{"start":{"date-parts":[[2019,8,1]],"date-time":"2019-08-01T00:00:00Z","timestamp":1564617600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100005825","name":"USDA | National Institute of Food and Agriculture","doi-asserted-by":"publisher","award":["2015-67015-23067"],"award-info":[{"award-number":["2015-67015-23067"]}],"id":[{"id":"10.13039\/100005825","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005825","name":"USDA | National Institute of Food and Agriculture","doi-asserted-by":"publisher","award":["2018-67015-28287"],"award-info":[{"award-number":["2018-67015-28287"]}],"id":[{"id":"10.13039\/100005825","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2019,8]]},"abstract":"<jats:p>PEDV is the most economically important porcine enteric viral pathogen and has caused immense economic losses in the pork industries in many countries. Effective and safe vaccines are desperately required but still not available. 2\u2032-<jats:italic>O<\/jats:italic>-MTase (nsp16) is highly conserved among coronaviruses (CoVs), and the inactivation of nsp16 in live attenuated vaccines has been attempted for several betacoronaviruses. We show that inactivation of both 2\u2032-<jats:italic>O<\/jats:italic>-MTase and the endocytosis signal of the spike protein is an approach to designing a promising live attenuated vaccine for PEDV. The<jats:italic>in vivo<\/jats:italic>passaging data also validated the stability of the KDKE<jats:sup>4A<\/jats:sup>-SYA mutant. KDKE<jats:sup>4A<\/jats:sup>-SYA warrants further evaluation in sows and their piglets and may be used as a platform for further optimization. Our findings further confirmed that nsp16 can be a universal target for CoV vaccine development and will aid in the development of vaccines against other emerging CoVs.<\/jats:p>","DOI":"10.1128\/jvi.00406-19","type":"journal-article","created":{"date-parts":[[2019,5,21]],"date-time":"2019-05-21T13:41:15Z","timestamp":1558446075000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":56,"title":["Engineering a Live Attenuated Porcine Epidemic Diarrhea Virus Vaccine Candidate via Inactivation of the Viral 2'-<i>O<\/i>-Methyltransferase and the Endocytosis Signal of the Spike Protein"],"prefix":"10.1128","volume":"93","author":[{"given":"Yixuan","family":"Hou","sequence":"first","affiliation":[{"name":"Food Animal Health Research Program, Ohio Agricultural Research and Development Center, College of Food, Agriculture and Environmental Sciences, The Ohio State University, Wooster, Ohio, USA"},{"name":"Department of Veterinary Preventive Medicine, College of Veterinary Medicine, The Ohio State University, Wooster, Ohio, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanzhong","family":"Ke","sequence":"additional","affiliation":[{"name":"Department of Pathobiology, College of Veterinary Medicine, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jineui","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Pathobiology, College of Veterinary Medicine, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6730-9729","authenticated-orcid":false,"given":"Dongwan","family":"Yoo","sequence":"additional","affiliation":[{"name":"Department of Pathobiology, College of Veterinary Medicine, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunfang","family":"Su","sequence":"additional","affiliation":[{"name":"Food Animal Health Research Program, Ohio Agricultural Research and Development Center, College of Food, Agriculture and Environmental Sciences, The Ohio State University, Wooster, Ohio, USA"},{"name":"Department of Veterinary Preventive Medicine, College of Veterinary Medicine, The Ohio State University, Wooster, Ohio, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"Boley","sequence":"additional","affiliation":[{"name":"Food Animal Health Research Program, Ohio Agricultural Research and Development Center, College of Food, Agriculture and Environmental Sciences, The Ohio State University, Wooster, Ohio, USA"},{"name":"Department of Veterinary Preventive Medicine, College of Veterinary Medicine, The Ohio State University, Wooster, Ohio, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juliet","family":"Chepngeno","sequence":"additional","affiliation":[{"name":"Food Animal Health Research Program, Ohio Agricultural Research and Development Center, College of Food, Agriculture and Environmental Sciences, The Ohio State University, Wooster, Ohio, USA"},{"name":"Department of Veterinary Preventive Medicine, College of Veterinary Medicine, The Ohio State University, Wooster, Ohio, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1447-6283","authenticated-orcid":false,"given":"Anastasia N.","family":"Vlasova","sequence":"additional","affiliation":[{"name":"Food Animal Health Research Program, Ohio Agricultural Research and Development Center, College of Food, Agriculture and Environmental Sciences, The Ohio State University, Wooster, Ohio, USA"},{"name":"Department of Veterinary Preventive Medicine, College of Veterinary Medicine, The Ohio State University, Wooster, Ohio, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda J.","family":"Saif","sequence":"additional","affiliation":[{"name":"Food Animal Health Research Program, Ohio Agricultural Research and Development Center, College of Food, Agriculture and Environmental Sciences, The Ohio State University, Wooster, Ohio, USA"},{"name":"Department of Veterinary Preventive Medicine, College of Veterinary Medicine, The Ohio State University, Wooster, Ohio, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiuhong","family":"Wang","sequence":"additional","affiliation":[{"name":"Food Animal Health Research Program, Ohio Agricultural Research and Development Center, College of Food, Agriculture and Environmental Sciences, The Ohio State University, Wooster, Ohio, USA"},{"name":"Department of Veterinary Preventive Medicine, College of Veterinary Medicine, The Ohio State University, Wooster, Ohio, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.3201\/eid1801.111259"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1177\/1040638713501675"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.3201\/eid1507.081256"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.2527\/jas.2015-9136"},{"key":"e_1_3_2_6_2","unstructured":"Paarlberg PL. 2014. Updated estimated economic welfare impacts of porcine epidemic diarrhea virus (PEDV). http:\/\/ageconsearch.umn.edu\/bitstream\/174517\/2\/14-4.Updated%20Estimated%20Economic%20Welfare%20Impacts%20of%20PEDV.pdf."},{"key":"e_1_3_2_7_2","doi-asserted-by":"crossref","first-page":"34","DOI":"10.54846\/jshap\/1030","article-title":"Serum and mammary secretion antibody responses in porcine epidemic diarrhea-immune gilts following porcine epidemic diarrhea vaccination","volume":"26","author":"Bjustrom-Kraft J","year":"2018","unstructured":"Bjustrom-Kraft J, Woodard K, Gim\u00e9nez-Lirola L, Setness B, Ji J, Lasley P, Nelson E, Zhang J, Baum D, Gauger P, Main R, Zimmerman J. 2018. Serum and mammary secretion antibody responses in porcine epidemic diarrhea-immune gilts following porcine epidemic diarrhea vaccination. J Swine Health Prod 26:34\u201340.","journal-title":"J Swine Health Prod"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13567-017-0472-z"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.virusres.2016.08.005"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.virusres.2016.05.016"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-animal-022114-111038"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.7774\/cevr.2015.4.2.166"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.prevetmed.2015.10.020"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00705-018-3968-6"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vetmic.2017.01.015"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2017.10.052"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.3390\/v9050121"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vetmic.2017.06.019"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12917-017-1283-1"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.3390\/v7102891"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12917-018-1756-x"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.virusres.2016.07.003"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00227-17"},{"key":"e_1_3_2_24_2","first-page":"445","volume-title":"Desk encyclopedia of general virology","author":"Baker SC","year":"2010","unstructured":"Baker SC. 2010. Coronavirus: molecular biology, p 445\u2013453. In Mahy BWJ, van Regenmortel MHV (ed), Desk encyclopedia of general virology. Academic Press, New York, NY."},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2015.01.019"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature09489"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00407-08"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1002294"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0808790106"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1508686112"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M114.577353"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1002059"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.03571-13"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1128\/mSphere.00346-17"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1979"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00710-18"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01758-18"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01677-17"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.antiviral.2017.01.012"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.3201\/eid2007.140296"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-018-0010-9"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.coviro.2018.12.001"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vetmic.2014.08.012"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13567-015-0278-9"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12917-016-0697-5"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-1119(02)01097-1"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00814-06"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02806-12"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1003521"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00876-14"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1100552108"},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms8090"},{"key":"e_1_3_2_53_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2015.12.010"},{"key":"e_1_3_2_54_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02000-18"},{"key":"e_1_3_2_55_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12985-015-0345-x"},{"key":"e_1_3_2_56_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01091-16"},{"key":"e_1_3_2_57_2","doi-asserted-by":"publisher","DOI":"10.1186\/1743-422X-10-26"},{"key":"e_1_3_2_58_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00700-14"},{"key":"e_1_3_2_59_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02514-15"},{"key":"e_1_3_2_60_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1005215"},{"key":"e_1_3_2_61_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13567-015-0249-1"},{"key":"e_1_3_2_62_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vetmic.2015.04.022"},{"key":"e_1_3_2_63_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0139266"},{"key":"e_1_3_2_64_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.meegid.2019.01.022"},{"key":"e_1_3_2_65_2","doi-asserted-by":"publisher","DOI":"10.1586\/erv.13.3"},{"key":"e_1_3_2_66_2","doi-asserted-by":"crossref","first-page":"1002","DOI":"10.2460\/ajvr.1998.59.08.1002","article-title":"Immune response of sows vaccinated with attenuated transmissible gastroenteritis virus (TGEV) and recombinant TGEV spike protein vaccines and protection of their suckling pigs against virulent TGEV challenge exposure","volume":"59","author":"Park S","year":"1998","unstructured":"Park S, Sestak K, Hodgins DC, Shoup DI, Ward LA, Jackwood DJ, Saif LJ. 1998. Immune response of sows vaccinated with attenuated transmissible gastroenteritis virus (TGEV) and recombinant TGEV spike protein vaccines and protection of their suckling pigs against virulent TGEV challenge exposure. Am J Vet Res 59:1002\u20131008.","journal-title":"Am J Vet Res"},{"key":"e_1_3_2_67_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2013.12.039"},{"key":"e_1_3_2_68_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1501705"},{"key":"e_1_3_2_69_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.00727"},{"key":"e_1_3_2_70_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.01451-15"},{"key":"e_1_3_2_71_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-7091-6553-9_17"},{"key":"e_1_3_2_72_2","doi-asserted-by":"publisher","DOI":"10.3201\/eid2004.131685"},{"key":"e_1_3_2_73_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vetmic.2018.11.025"},{"key":"e_1_3_2_74_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2018.09.008"},{"key":"e_1_3_2_75_2","doi-asserted-by":"publisher","DOI":"10.1006\/meth.2001.1262"}],"container-title":["Journal of Virology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/JVI.00406-19","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/JVI.00406-19","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,7,18]],"date-time":"2024-07-18T10:03:21Z","timestamp":1721297001000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/JVI.00406-19"}},"subtitle":[],"editor":[{"given":"Tom","family":"Gallagher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2019,8]]},"references-count":74,"journal-issue":{"issue":"15","published-print":{"date-parts":[[2019,8]]}},"alternative-id":["10.1128\/JVI.00406-19"],"URL":"https:\/\/doi.org\/10.1128\/jvi.00406-19","relation":{},"ISSN":["0022-538X","1098-5514"],"issn-type":[{"value":"0022-538X","type":"print"},{"value":"1098-5514","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,8]]},"assertion":[{"value":"2019-03-07","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-05-13","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-07-17","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e00406-19"}}