A Mouse Model for Human Norovirus

ABSTRACT Human 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...

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Autores principales:	Stefan Taube, Abimbola O. Kolawole, Marina Höhne, John E. Wilkinson, Scott A. Handley, Jeffrey W. Perry, Larissa B. Thackray, Ramesh Akkina, Christiane E. Wobus
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2013
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/d7a2d9876efd4f31931c45525e64de71
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spelling	oai:doaj.org-article:d7a2d9876efd4f31931c45525e64de712021-11-15T15:43:09ZA Mouse Model for Human Norovirus10.1128/mBio.00450-132150-7511https://doaj.org/article/d7a2d9876efd4f31931c45525e64de712013-08-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00450-13https://doaj.org/toc/2150-7511ABSTRACT Human 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.Stefan TaubeAbimbola O. KolawoleMarina HöhneJohn E. WilkinsonScott A. HandleyJeffrey W. PerryLarissa B. ThackrayRamesh AkkinaChristiane E. WobusAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 4, Iss 4 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Stefan Taube Abimbola O. Kolawole Marina Höhne John E. Wilkinson Scott A. Handley Jeffrey W. Perry Larissa B. Thackray Ramesh Akkina Christiane E. Wobus A Mouse Model for Human Norovirus
description	ABSTRACT Human 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.
format	article
author	Stefan Taube Abimbola O. Kolawole Marina Höhne John E. Wilkinson Scott A. Handley Jeffrey W. Perry Larissa B. Thackray Ramesh Akkina Christiane E. Wobus
author_facet	Stefan Taube Abimbola O. Kolawole Marina Höhne John E. Wilkinson Scott A. Handley Jeffrey W. Perry Larissa B. Thackray Ramesh Akkina Christiane E. Wobus
author_sort	Stefan Taube
title	A Mouse Model for Human Norovirus
title_short	A Mouse Model for Human Norovirus
title_full	A Mouse Model for Human Norovirus
title_fullStr	A Mouse Model for Human Norovirus
title_full_unstemmed	A Mouse Model for Human Norovirus
title_sort	mouse model for human norovirus
publisher	American Society for Microbiology
publishDate	2013
url	https://doaj.org/article/d7a2d9876efd4f31931c45525e64de71
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A Mouse Model for Human Norovirus

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