Abstract

Accumulating studies show that the host microbiome influences the development or progression of many diseases. The eukaryotic virome, as a key component of the microbiome, plays an important role in host health and disease in humans and animals, including research animals designed to model human disease. To date, the majority of research on the microbiome has focused on bacterial populations, while less attention has been paid to the viral component. Members of the eukaryotic virome interact with the commensal bacterial microbiome through trans-kingdom interactions, and influence host immunity and disease phenotypes as a collective microbial ecosystem. As such, differences in the virome may affect the reproducibility of animal models, and supplementation of the virome may enhance the translatability of animal models of human disease. However, there are minimal empirical data regarding differences in the virome of mice from different commercial sources. Our hypotheses were that the mice obtained from pet store sources and lab mice differ in their eukaryotic virome, and that lab mice from different sources would also have different viromes. To test this hypothesis, the ViroCap platform was used to characterize the eukaryotic virome in multiple tissues of mice from different sources including three sources of laboratory mice and two pet stores. As expected, pet store mice harbored a much greater diversity within the virome compared to lab mice. This included an ostensibly novel norovirus strain identified in one source of these mice. Viruses found in both laboratory and pet store populations included four strains of endogenous retroviruses and murine astrovirus with the latter being restricted to one source of lab mice. Considering the relatively high richness virome within different samples from healthy humans, these data suggest that mouse models from alternative sources may be more translational to the human condition. Moreover, these data demonstrate that, by characterizing the eukaryotic murine virome from different sources, novel viruses may be identified for use as field strains in biomedical research.

Highlights

  • Licensee MDPI, Basel, Switzerland.Animal models, especially mouse models, are used in biomedical research to investigate conditions and acute conditions.While the advantages of using mouse models are appreciated, there are limitations to be considered in terms of their reproducibility and accurate recapitulation of the human conditions they are used to study [1,2,3,4]

  • This example of therapeutic failure of a promising drug during clinical trials, combined with other study results [6,7,8] related to the reproducibility or translatability of rodent studies, suggests a need for a more thorough characterization and consideration of the mouse models used in biomedical research

  • A subjective review of viruses detected in each group of mice revealed two clear patterns

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Summary

Introduction

Licensee MDPI, Basel, Switzerland.Animal models, especially mouse models, are used in biomedical research to investigate conditions (including chronic diseases such as autoimmune diseases, cancer, human immunodeficiency virus infection) and acute conditions (such as many infectious diseases).While the advantages of using mouse models are appreciated, there are limitations to be considered in terms of their reproducibility and accurate recapitulation of the human conditions they are used to study [1,2,3,4]. Microorganisms 2021, 9, 2064 that worked very well in experimental treatment in an established mouse model of human amyotrophic lateral sclerosis (ALS) disease [5] was unable to reproduce these preclinical results when applied to a human population [3]. This example of therapeutic failure of a promising drug during clinical trials, combined with other study results [6,7,8] related to the reproducibility or translatability of rodent studies, suggests a need for a more thorough characterization and consideration of the mouse models used in biomedical research

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