Natural rodent model of viral transmission reveals biological features of virus population dynamics

Emerging viruses threaten global health, but few experimental models can characterize the virus and host factors necessary for within- and cross-species transmission. Here, we leverage a model whereby pet store mice or rats-which harbor natural rodent pathogens-are cohoused with laboratory mice. Thi...

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Published inThe Journal of experimental medicine Vol. 219; no. 2
Main Authors Fay, Elizabeth J, Balla, Keir M, Roach, Shanley N, Shepherd, Frances K, Putri, Dira S, Wiggen, Talia D, Goldstein, Stephen A, Pierson, Mark J, Ferris, Martin T, Thefaine, Claire E, Tucker, Andrew, Salnikov, Mark, Cortez, Valerie, Compton, Susan R, Kotenko, Sergei V, Hunter, Ryan C, Masopust, David, Elde, Nels C, Langlois, Ryan A
Format Journal Article
LanguageEnglish
Published United States Rockefeller University Press 27.12.2021
Subjects
Animal Diseases - transmission
Animal Diseases - virology
Animals
Biomarkers
Disease Models, Animal
Disease Susceptibility
Host-Pathogen Interactions
Humans
Infectious Disease and Host Defense
Interferons - metabolism
Mice
Mice, Knockout
Microbial Interactions
Rodentia
Virus Diseases - etiology
Virus Diseases - metabolism
Virus Diseases - transmission
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Summary:Emerging viruses threaten global health, but few experimental models can characterize the virus and host factors necessary for within- and cross-species transmission. Here, we leverage a model whereby pet store mice or rats-which harbor natural rodent pathogens-are cohoused with laboratory mice. This "dirty" mouse model offers a platform for studying acute transmission of viruses between and within hosts via natural mechanisms. We identified numerous viruses and other microbial species that transmit to cohoused mice, including prospective new members of the Coronaviridae, Astroviridae, Picornaviridae, and Narnaviridae families, and uncovered pathogen interactions that promote or prevent virus transmission. We also evaluated transmission dynamics of murine astroviruses during transmission and spread within a new host. Finally, by cohousing our laboratory mice with the bedding of pet store rats, we identified cross-species transmission of a rat astrovirus. Overall, this model system allows for the analysis of transmission of natural rodent viruses and is a platform to further characterize barriers to zoonosis.
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Disclosures:   S.V. Kotenko reported a patent to IFN-λ polypeptides and compositions issued, a patent to IFN-λ1 polypeptides issued, a patent to method for increasing IFN activity in an individual issued, a patent to methods for increasing levels of IFN activity with an IFN-λ3 polypeptide issued, and a patent to type I and type III IFN fusion molecules and methods for use thereof pending. No other disclosures were reported.
E.J. Fay, K.M. Balla, S.N. Roach, and F.K. Shepherd contributed equally to this paper.
ISSN:0022-1007
1540-9538
DOI:10.1084/jem.20211220