Diversity of Murine Norovirus Strains Isolated from Asymptomatic Mice of Different Genetic Backgrounds within a Single U.S. Research Institute

Elyssa L Barron,Victor Prikhodko,Kim Y Green,Kathy Perdue,Carlos Sandoval-Jaime,Karin Bok,Kim Hasenkrug,Jerrold M Ward,Aaron B Carmody,Crystal R Rhodes,Stanislav V Sosnovtsev,Karol Sestak

doi:10.1371/journal.pone.0021435

Elyssa L Barron, Victor Prikhodko + Show 10 more

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https://doi.org/10.1371/journal.pone.0021435

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Abstract

Antibody prevalence studies in laboratory mice indicate that murine norovirus (MNV) infections are common, but the natural history of these viruses has not been fully established. This study examined the extent of genetic diversity of murine noroviruses isolated from healthy laboratory mice housed in multiple animal facilities within a single, large research institute- the National Institute of Allergy and Infectious Diseases of the National Institutes of Health (NIAID-NIH) in Bethesda, Maryland, U.S. Ten distinct murine norovirus strains were isolated from various tissues and feces of asymptomatic wild type sentinel mice as well as asymptomatic immunodeficient (RAG 2−/−) mice. The NIH MNV isolates showed little cytopathic effect in permissive RAW264.7 cells in early passages, but all isolates examined could be adapted to efficient growth in cell culture by serial passage. The viruses, although closely related in genome sequence, were distinguishable from each other according to facility location, likely due to the introduction of new viruses into each facility from separate sources or vendors at different times. Our study indicates that the murine noroviruses are widespread in these animal facilities, despite rigorous guidelines for animal care and maintenance.

Highlights

Noroviruses, members of the virus family Caliciviridae, are ubiquitous enteric viruses found in a broad range of animal species, including mice [1]
By serologic screening of sentinel mice housed in several National Institute of Allergy and Infectious Diseases (NIAID) animal facilities, we found evidence initially for norovirus infection, and in addition, we were able to detect the virus by RT-PCR in representative mice [15]
Murine noroviruses are associated with asymptomatic infection and shedding in many mouse strains, making the viruses difficult to detect in animals without active screening [13]

Summary

Introduction

Noroviruses, members of the virus family Caliciviridae, are ubiquitous enteric viruses found in a broad range of animal species, including mice [1]. In humans, they are associated with nausea, vomiting, diarrhea, and fever that characteristically last approximately 24–48 hours. They are associated with nausea, vomiting, diarrhea, and fever that characteristically last approximately 24–48 hours They are transmitted via person-toperson contact, or by exposure to contaminated food or water. The approximately 7.6 kb positive-sense, single-stranded RNA genome of norovirus is organized into three major open-reading frames (ORFs): ORF1 encodes a large polyprotein that is cleaved into nonstructural precursors and proteins involved in viral replication; ORF2 encodes the major capsid protein, VP1; and ORF3 encodes a minor structural protein of the virion, VP2 [3,4,5,6]. Noroviruses have been divided into five distinct genogroups (GI– GV) [9], with human pathogens belonging to GI, GII, and GIV

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