Increased and prolonged human norovirus infection in RAG2/IL2RG deficient gnotobiotic pigs with severe combined immunodeficiency

Simple item page
dc.contributor.authorLei, Shaohuaen
dc.contributor.authorRyu, Junghyunen
dc.contributor.authorWen, Keen
dc.contributor.authorTwitchell, Ericaen
dc.contributor.authorBui, Tammyen
dc.contributor.authorRamesh, Ashwinen
dc.contributor.authorWeiss, Mariahen
dc.contributor.authorLi, Guohuaen
dc.contributor.authorSamuel, Helenen
dc.contributor.authorClark-Deener, Sherrieen
dc.contributor.authorJiang, Xien
dc.contributor.authorLee, Kihoen
dc.contributor.authorYuan, Lijuanen
dc.contributor.departmentAnimal and Poultry Sciencesen
dc.contributor.departmentBiomedical Sciences and Pathobiologyen
dc.contributor.departmentLarge Animal Clinical Sciencesen
dc.date.accessioned2017-02-22T15:40:30Zen
dc.date.available2017-02-22T15:40:30Zen
dc.date.issued2016-04-27en
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
dc.description.versionPublished versionen
dc.format.extent? - ? (12) page(s)en
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.1038/srep25222en
dc.identifier.issn2045-2322en
dc.identifier.orcidClark-Deener, S [0000-0002-6620-0625]en
dc.identifier.orcidYuan, Lijuan [0000-0003-0709-5228]en
dc.identifier.urihttp://hdl.handle.net/10919/75127en
dc.identifier.volume6en
dc.language.isoenen
dc.publisherNature Publishing Groupen
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
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectblood group antigenen
dc.subjectone-step generationen
dc.subjectin-vivoen
dc.subjectimmunocompromised patientsen
dc.subjectvaccine developmenten
dc.subjectunited-statesen
dc.subjectknockout pigsen
dc.subjectb-cellsen
dc.subjectgastroenteritisen
dc.subjectgeneen
dc.titleIncreased and prolonged human norovirus infection in RAG2/IL2RG deficient gnotobiotic pigs with severe combined immunodeficiencyen
dc.title.serialScientific Reportsen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten
pubs.organisational-group/Virginia Techen
pubs.organisational-group/Virginia Tech/Agriculture & Life Sciencesen
pubs.organisational-group/Virginia Tech/Agriculture & Life Sciences/Animal and Poultry Sciencesen
pubs.organisational-group/Virginia Tech/Agriculture & Life Sciences/CALS T&R Facultyen
pubs.organisational-group/Virginia Tech/All T&R Facultyen
pubs.organisational-group/Virginia Tech/Faculty of Health Sciencesen
pubs.organisational-group/Virginia Tech/Veterinary Medicineen
pubs.organisational-group/Virginia Tech/Veterinary Medicine/Biomedical Sciences and Pathobiologyen
pubs.organisational-group/Virginia Tech/Veterinary Medicine/CVM T&R Facultyen
pubs.organisational-group/Virginia Tech/Veterinary Medicine/Large Animal Clinical Sciencesen

Files

Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
Increased and prolonged human norovirus infection in RAG2/IL2RG deficient gnotobiotic pigs with severe combined immunodeficiency.pdf
Size:
1.67 MB
Format:
Adobe Portable Document Format
Description:
Published version
Download
License bundle
Now showing 1 - 1 of 1
Name:
VTUL_Distribution_License_2016_05_09.pdf
Size:
18.09 KB
Format:
Adobe Portable Document Format
Description:
Download

Collections

All Faculty Deposits
Scholarly Works, Biomedical Sciences and Pathobiology
Scholarly Works, Large Animal Clinical Sciences
Scholarly Works, School of Animal Sciences