A neonatal gnotobiotic pig model of human enterovirus 71 infection and associated immune responses

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dc.contributor.authorYang, Xingdongen
dc.contributor.authorLi, Guohuaen
dc.contributor.authorWen, Keen
dc.contributor.authorBui, Tammyen
dc.contributor.authorLiu, Fangningen
dc.contributor.authorKocher, Jacoben
dc.contributor.authorJortner, Bernard S.en
dc.contributor.authorVonck, Marliceen
dc.contributor.authorPelzer, Kevin D.en
dc.contributor.authorDeng, Jieen
dc.contributor.authorZhu, Runanen
dc.contributor.authorLi, Yuyunen
dc.contributor.authorQian, Yuanen
dc.contributor.authorYuan, Lijuanen
dc.date.accessioned2017-02-22T15:35:48Zen
dc.date.available2017-02-22T15:35:48Zen
dc.date.issued2014-05-21en
dc.description.abstractVaccine development and pathogenesis studies for human enterovirus 71 are limited by a lack of suitable animal models. Here, we report the development of a novel neonatal gnotobiotic pig model using the non-pig-adapted neurovirulent human enterovirus 71 strain BJ110, which has a C4 genotype. Porcine small intestinal epithelial cells, peripheral blood mononuclear cells and neural cells were infected in vitro. Oral and combined oral–nasal infection of 5-day-old neonatal gnotobiotic pigs with 53108 fluorescence forming units (FFU) resulted in shedding up to 18 days post-infection, with viral titers in rectal swab samples peaking at 2.223108 viral RNA copies/mL. Viral capsid proteins were detected in enterocytes within the small intestines on post-infection days (PIDs) 7 and 14. Additionally, viral RNA was detected in intestinal and extra-intestinal tissues, including the central nervous system, the lung and cardiac muscle. The infected neonatal gnotobiotic pigs developed fever, forelimb weakness, rapid breathing and some hand, foot and mouth disease symptoms. Flow cytometry analysis revealed increased frequencies of both CD41 and CD81 IFN-c-producing T cells in the brain and the blood on PID 14, but reduced frequencies were observed in the lung. Furthermore, high titers of serum virus-neutralizing antibodies were generated in both orally and combined oral–nasally infected pigs on PIDs 7, 14, 21 and 28. Together, these results demonstrate that neonatal gnotobiotic pigs represent a novel animal model for evaluating vaccines for human enterovirus 71 and for understanding the pathogenesis of this virus and the associated immune responses.en
dc.description.versionPublished versionen
dc.format.extent? - ? (12) page(s)en
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.1038/emi.2014.35en
dc.identifier.issn2222-1751en
dc.identifier.urihttp://hdl.handle.net/10919/75123en
dc.identifier.volume3en
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:000339238200002&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=930d57c9ac61a043676db62af60056c1en
dc.rightsCreative Commons Attribution-NonCommercial-ShareAlike 3.0 Unporteden
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/3.0/en
dc.subjectImmunologyen
dc.subjectMicrobiologyen
dc.subjectadaptive immune responsesen
dc.subjectanimal modelen
dc.subjecthuman enterovirus 71en
dc.subjectneonatal gnotobiotic pigsen
dc.subjectpathogenesisen
dc.subjectvaccine evaluationen
dc.subjectSELECTIN GLYCOPROTEIN LIGAND-1en
dc.subjectBRAIN-STEM ENCEPHALITISen
dc.subjectHUMAN ROTAVIRUSen
dc.subjectMOUTH-DISEASEen
dc.subjectANTIBODY-RESPONSESen
dc.subjectCYNOMOLGUS MONKEYSen
dc.subjectCLINICAL-FEATURESen
dc.subjectCELL RESPONSESen
dc.subjectSUBGENOTYPE C4en
dc.subjectRHESUS-MONKEYSen
dc.titleA neonatal gnotobiotic pig model of human enterovirus 71 infection and associated immune responsesen
dc.title.serialEmerging Microbes & Infectionsen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten
pubs.organisational-group/Virginia Techen
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

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