Identification of an Astrovirus Commonly Infecting Laboratory Mice in the US and Japan

Abstract

Mice (Mus musculus) are the most commonly used laboratory animals. Viral metagenomics on tissues of immunodeficient mice revealed sequences of a novel mammalian astrovirus. Using PCR, we screened mice from 4 breeders, 4 pharmaceutical companies, 14 research institutes and 30 universities in the US and Japan. Mice from one US breeder tested positive while none from Japanese breeders were positive for MuAstV. Mice in over half of the universities (19/30), institutes (7/14) and pharmaceutical animal facilities (2/4) investigated revealed the presence of MuAstV. Nine mice strains tested positive including both immunodeficient strains (NSG, NOD-SCID, NSG-3GS, C57BL6-Timp-3 −/−, and uPA-NOG) and immunocompetent strains (B6J, ICR, Bash2, BALB/c). Our data indicates that MuAstV has a wide geographical, institutional and host strain distribution. Comparison of the MuAstV RdRp sequences showed numerous mutations indicating ongoing viral divergence in different facilities. This study demonstrates the need for metagenomic screening of laboratory animals to identify adventitious infections that may affect experimental outcomes.

Indigenous house mice dominate small mammal communities in northern Afghan military bases

“…As they are RNA viruses, murine astroviruses are in general prone to a high sequence variability driven by the lacking proof-reading function of the RdRp as well as specific features of the astrovirus genome. In addition, these viruses are also capable of genomic recombination which has already been described for human astroviruses [50,51]. In the case of this study, two different genotypes of astroviruses were detected each in house mice from Afghanistan and Germany.…”

“…For that purpose, astroviruses were selected as an example of a ssRNA virus frequently detected in rodents and more specifically in house mice [48][49][50]. As they are RNA viruses, murine astroviruses are in general prone to a high sequence variability driven by the lacking proof-reading function of the RdRp as well as specific features of the astrovirus genome.…”

A diverse group of small circular ssDNA viral genomes in human and non-human primate stools

“…2012, 2013b). Sequence data were analyzed by a customized NGS pipeline as described previously (Deng et al.…”

Human Astroviruses

“…Surprisingly, it has recently been recognized that MuAstVs are commonly found infecting laboratory mice in different countries, including breeding facilities, research institutions, and commercial research mouse facilities (100,153,192,193) (Fig. 6, purple).…”

“…6, purple). Although the mice are asymptomatic, the viruses have been isolated in the gastrointestinal tracts and mesenteric lymph nodes of wild-type mice but also in spleens, livers, and kidneys of immunodeficient mice (100,192).…”