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dc.contributor.authorLei, Shaohuaen_US
dc.contributor.authorRyu, Junghyunen_US
dc.contributor.authorWen, Keen_US
dc.contributor.authorTwitchell, Ericaen_US
dc.contributor.authorBui, Tammyen_US
dc.contributor.authorRamesh, Ashwinen_US
dc.contributor.authorWeiss, Mariahen_US
dc.contributor.authorLi, Guohuaen_US
dc.contributor.authorSamuel, Helenen_US
dc.contributor.authorClark-Deener, Sherrieen_US
dc.contributor.authorJiang, Xien_US
dc.contributor.authorLee, Kihoen_US
dc.contributor.authorYuan, Lijuanen_US
dc.date.accessioned2017-02-22T15:40:30Z
dc.date.available2017-02-22T15:40:30Z
dc.date.issued2016-04-27en_US
dc.identifier.issn2045-2322en_US
dc.identifier.urihttp://hdl.handle.net/10919/75127
dc.description.abstractApplication of genetically engineered (GE) large animals carrying multi-allelic modifications has been hampered by low efficiency in production and extended gestation period compared to rodents. Here, we rapidly generated RAG2/IL2RG double knockout pigs using direct injection of CRISPR/Cas9 system into developing embryos. RAG2/IL2RG deficient pigs were immunodeficient, characterized by depletion of lymphocytes and either absence of or structurally abnormal immune organs. Pigs were maintained in gnotobiotic facility and evaluated for human norovirus (HuNoV) infection. HuNoV shedding lasted for 16 days in wild type pigs, compared to 27 days (until the end of trials) in RAG2/IL2RG deficient pigs. Additionally, higher HuNoV titers were detected in intestinal tissues and contents and in blood, indicating increased and prolonged HuNoV infection in RAG2/IL2RG deficient pigs and the importance of lymphocytes in HuNoV clearance. These results suggest that GE immunodeficient gnotobiotic pigs serve as a novel model for biomedical research and will facilitate HuNoV studies.en_US
dc.format.extent? - ? (12) page(s)en_US
dc.languageEnglishen_US
dc.publisherNature Publishing Groupen_US
dc.relation.urihttp://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000374857900001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=930d57c9ac61a043676db62af60056c1en_US
dc.subjectMultidisciplinary Sciencesen_US
dc.subjectScience & Technology - Other Topicsen_US
dc.subjectBLOOD GROUP ANTIGENen_US
dc.subjectONE-STEP GENERATIONen_US
dc.subjectIN-VIVOen_US
dc.subjectIMMUNOCOMPROMISED PATIENTSen_US
dc.subjectVACCINE DEVELOPMENTen_US
dc.subjectUNITED-STATESen_US
dc.subjectKNOCKOUT PIGSen_US
dc.subjectB-CELLSen_US
dc.subjectGASTROENTERITISen_US
dc.subjectGENEen_US
dc.titleIncreased and prolonged human norovirus infection in RAG2/IL2RG deficient gnotobiotic pigs with severe combined immunodeficiencyen_US
dc.typeArticle - Refereed
dc.description.versionPublished (Publication status)en_US
dc.title.serialSCIENTIFIC REPORTSen_US
dc.identifier.doihttps://doi.org/10.1038/srep25222
dc.identifier.volume6en_US
dc.identifier.orcidClark-Deener, S [0000-0002-6620-0625]en_US
pubs.organisational-group/Virginia Tech
pubs.organisational-group/Virginia Tech/Agriculture & Life Sciences
pubs.organisational-group/Virginia Tech/Agriculture & Life Sciences/Animal and Poultry Sciences
pubs.organisational-group/Virginia Tech/Agriculture & Life Sciences/CALS T&R Faculty
pubs.organisational-group/Virginia Tech/All T&R Faculty
pubs.organisational-group/Virginia Tech/Faculty of Health Sciences
pubs.organisational-group/Virginia Tech/Veterinary Medicine
pubs.organisational-group/Virginia Tech/Veterinary Medicine/Biomedical Sciences and Pathobiology
pubs.organisational-group/Virginia Tech/Veterinary Medicine/CVM T&R Faculty
pubs.organisational-group/Virginia Tech/Veterinary Medicine/Large Animal Clinical Sciences


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