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2013-07-16Zeitschriftenartikel DOI: 10.1128/mBio.00450-13
A Mouse Model for Human Norovirus
dc.contributor.authorTaube, Stefan
dc.contributor.authorKolawole, Abimbola O.
dc.contributor.authorHöhne, Marina
dc.contributor.authorWilkinson, John E.
dc.contributor.authorHandley, Scott A.
dc.contributor.authorPerry, Jeffrey W.
dc.contributor.authorThackray, Larissa B.
dc.contributor.authorAkkina, Ramesh
dc.contributor.authorWobus, Christiane E.
dc.date.accessioned2018-05-07T16:54:03Z
dc.date.available2018-05-07T16:54:03Z
dc.date.created2013-07-29
dc.date.issued2013-07-16none
dc.identifier.otherhttp://edoc.rki.de/oa/articles/reR75PiwRWiTU/PDF/21ZZ7zpWCCZfY.pdf
dc.identifier.urihttp://edoc.rki.de/176904/1625
dc.description.abstractHuman noroviruses (HuNoVs) cause significant morbidity and mortality worldwide. However, despite substantial efforts, a small-animal model for HuNoV has not been described to date. Since "humanized" mice have been successfully used to study human-tropic pathogens in the past, we challenged BALB/c mice deficient in recombination activation gene (Rag) 1 or 2 and common gamma chain (γc) (Rag-γc) engrafted with human CD34(+) hematopoietic stem cells, nonengrafted siblings, and immunocompetent wild-type controls with pooled stool isolates from patients positive for HuNoV. Surprisingly, both humanized and nonhumanized BALB/c Rag-γc-deficient mice supported replication of a GII.4 strain of HuNoV, as indicated by increased viral loads over input. In contrast, immunocompetent wild-type BALB/c mice were not infected. An intraperitoneal route of infection and the BALB/c genetic background were important for facilitating a subclinical HuNoV infection of Rag-γc-deficient mice. Expression of structural and nonstructural proteins was detected in cells with macrophage-like morphology in the spleens and livers of BALB/c Rag-γc-deficient mice, confirming the ability of HuNoV to replicate in a mouse model. In summary, HuNoV replication in BALB/c Rag-γc-deficient mice is dependent on the immune-deficient status of the host but not on the presence of human immune cells and provides the first genetically manipulable small-animal model for studying HuNoV infection. IMPORTANCE Human noroviruses are a significant cause of viral gastroenteritis worldwide, resulting in significant morbidity and mortality. Antivirals and vaccines are currently not available, in part due to the inability to study these viruses in a genetically manipulable, small-animal model. Herein, we report the first mouse model for human noroviruses. This model will accelerate our understanding of human norovirus biology and provide a useful resource for evaluating antiviral therapies.eng
dc.language.isoeng
dc.publisherRobert Koch-Institut
dc.subjectViral/geneticseng
dc.subjectAnimalseng
dc.subjectHumanseng
dc.subjectMolecular Sequence Dataeng
dc.subjectMiceeng
dc.subjectDisease Models Animaleng
dc.subjectMice Knockouteng
dc.subjectGenome Viraleng
dc.subjectLiver/virologyeng
dc.subjectViral Loadeng
dc.subjectCaliciviridae Infections/pathologyeng
dc.subjectCaliciviridae Infections/virologyeng
dc.subjectFeces/virologyeng
dc.subjectMacrophages/virologyeng
dc.subjectMice Inbred BALB Ceng
dc.subjectMice SCIDeng
dc.subjectNorovirus/geneticseng
dc.subjectNorovirus/growth & developmenteng
dc.subjectNorovirus/isolation & purificationeng
dc.subjectNorovirus/pathogenicityeng
dc.subjectRNAeng
dc.subjectSequence Analysi DNAeng
dc.subjectSpleen/virologyeng
dc.subject.ddc610 Medizin
dc.titleA Mouse Model for Human Norovirus
dc.typeperiodicalPart
dc.identifier.urnurn:nbn:de:0257-10032233
dc.identifier.doi10.1128/mBio.00450-13
dc.identifier.doihttp://dx.doi.org/10.25646/1550
local.edoc.container-titlemBio
local.edoc.container-textTaube S, Kolawole AO, Höhne M, Wilkinson JE, Handley SA, Perry JW, Thackray LB, Akkina R, Wobus CE. 2013. A mouse model for human norovirus. mBio 4(4):e00450- 13.
local.edoc.fp-subtypeArtikel
local.edoc.type-nameZeitschriftenartikel
local.edoc.container-typeperiodical
local.edoc.container-type-nameZeitschrift
local.edoc.container-urlhttp://mbio.asm.org/content/4/4/e00450-13.long
local.edoc.container-publisher-nameAmerican Society for Microbiology
local.edoc.container-volume4
local.edoc.container-issue4
local.edoc.container-year2013

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