title: A Gnotobiotic Pig Model for Determining Human Norovirus Inactivation by High-Pressure Processing.
abstract: Human norovirus (NoV) is responsible for over 90% of outbreaks of acute nonbacterial gastroenteritis worldwide and accounts for 60% of cases of foodborne illness in the United States. Currently, the infectivity of human NoVs is poorly understood due to the lack of a cell culture system. In this study, we determined the survival of a human NoV genogroup II, genotype 4 (GII.4) strain in seeded oyster homogenates after high-pressure processing (HPP) using a novel receptor binding assay and a gnotobiotic pig model. Pressure conditions of 350 MPa at 0°C for 2 min led to a 3.7-log10 reduction in the number of viral RNA copies in oysters, as measured by the porcine gastric mucin-conjugated magnetic bead (PGM-MB) binding assay and real-time RT-PCR, whereas pressure conditions of 350 MPa at 35°C for 2 min achieved only a 1-log10 reduction in the number of RNA copies. Newborn gnotobiotic piglets orally fed oyster homogenate treated at 350 MPa and 0°C for 2 min did not have viral RNA shedding in feces, histologic lesions, or viral replication in the small intestine. In contrast, gnotobiotic piglets fed oysters treated at 350 MPa and 35°C for 2 min had high levels of viral shedding in feces and exhibited significant histologic lesions and viral replication in the small intestine. Collectively, these data demonstrate that (i) human NoV survival estimated by an in vitro PGM-MB virus binding assay is consistent with the infectivity determined by an in vivo gnotobiotic piglet model and (ii) HPP is capable of inactivating a human NoV GII.4 strain at commercially acceptable pressure levels.
authors.affiliation: Department of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, Columbus, Ohio, USA Program in Food Science and Technology, The Ohio State University, Columbus, Ohio, USA.
authors.forename: Fangfei
authors.initials: F
authors.lastname: Lou
authors.affiliation: Department of Animal and Food Sciences, University of Delaware, Newark, Delaware, USA.
authors.forename: Mu
authors.initials: M
authors.lastname: Ye
authors.affiliation: Department of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, Columbus, Ohio, USA.
authors.forename: Yuanmei
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Department of Animal and Food Sciences, University of Delaware, Newark, Delaware, USA.
authors.forename: Xinhui
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, Columbus, Ohio, USA.
authors.forename: Erin
authors.initials: E
authors.lastname: DiCaprio
authors.affiliation: Department of Animal and Food Sciences, University of Delaware, Newark, Delaware, USA.
authors.forename: Haiqiang
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, Columbus, Ohio, USA.
authors.forename: Steven
authors.initials: S
authors.lastname: Krakowka
authors.affiliation: Department of Molecular Virology, Immunology and Medical Genetics, The Ohio State University, Columbus, Ohio, USA.
authors.forename: John
authors.initials: J
authors.lastname: Hughes
authors.affiliation: U.S. Department of Agriculture, Agricultural Research Service, Food Safety and Intervention Technologies Research Unit, James W. W. Baker Center, Delaware State University, Dover, Delaware, USA.
authors.forename: David
authors.initials: D
authors.lastname: Kingsley
authors.affiliation: Department of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, Columbus, Ohio, USA li.926@osu.edu.
authors.forename: Jianrong
authors.initials: J
authors.lastname: Li
mesh_terms: D000818:Animals; D017250:Caliciviridae Infections / Q000821:virology*; D004195:Disease Models, Animal; D005506:Food Contamination / Q000517:prevention & control; D005511:Food Handling / Q000295:instrumentation / Q000379:methods*; D005517:Foodborne Diseases / Q000821:virology*; D005856:Germ-Free Life; D006801:Humans; D029322:Norovirus / Q000737:chemistry / Q000502:physiology*; D010125:Ostreidae / Q000821:virology*; D011312:Pressure; D012758:Shellfish / Q000821:virology*; D013552:Swine; D038301:Virus Inactivation