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Enteric viruses evoke broad host immune responses resembling bacterial microbiome

Dallari Simone, Heaney Thomas, Rosas-Villegas Adriana, Jessica A. Neil, Wong Serre-Yu, Judy J. Brown, Urbanek Kelly, Terence S. Dermody, Cadwell Ken
doi: https://doi.org/10.1101/2020.10.20.347286
Dallari Simone
1Kimmel Center for Biology and Medicine at the Skirball Institute, New York University Grossman School of Medicine, New York, NY, 10016, USA
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Heaney Thomas
1Kimmel Center for Biology and Medicine at the Skirball Institute, New York University Grossman School of Medicine, New York, NY, 10016, USA
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Rosas-Villegas Adriana
1Kimmel Center for Biology and Medicine at the Skirball Institute, New York University Grossman School of Medicine, New York, NY, 10016, USA
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Jessica A. Neil
1Kimmel Center for Biology and Medicine at the Skirball Institute, New York University Grossman School of Medicine, New York, NY, 10016, USA
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Wong Serre-Yu
1Kimmel Center for Biology and Medicine at the Skirball Institute, New York University Grossman School of Medicine, New York, NY, 10016, USA
2Department of Medicine, Henry D. Janowitz Division of Gastroenterology, Susan and Leonard Feinstein Inflammatory Bowel Disease Center, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America
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Judy J. Brown
3Department of Pathology, Microbiology, and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA
4Department of Biology, Trevecca Nazarene University, Nashville, Tennessee, USA
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Urbanek Kelly
5Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
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Terence S. Dermody
5Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
6Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
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Cadwell Ken
1Kimmel Center for Biology and Medicine at the Skirball Institute, New York University Grossman School of Medicine, New York, NY, 10016, USA
7Department of Microbiology, New York University Grossman School of Medicine, New York, NY 10016, USA
8Division of Gastroenterology and Hepatology, Department of Medicine, New York University Langone Health, New York, NY 10016, USA
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  • For correspondence: Ken.Cadwell@med.nyu.edu
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SUMMARY

Contributions of the viral component of the microbiome, the virome, to the development of innate and adaptive immunity are largely unknown. Here, we systematically defined the host response in mice to a panel of eukaryotic enteric viruses representing six different families. Most of these viruses asymptomatically infected the mice, the magnitude and duration of which was dependent on the microbiota. Flow cytometric and transcriptional profiling of mice mono-associated with these viruses unveiled general adaptations by the host, such as lymphocyte differentiation and IL-22 signatures in the intestine as well as numerous viral strain-specific responses that persist. Comparison with a dataset derived from analogous bacterial mono-association mice identified bacterial species that evoke an immune response comparable to the viruses we examined. These results expand an understanding of the immune space occupied by the enteric virome and underscore the importance of viral exposure events.

Competing Interest Statement

K.C. receives research funding from Pfizer and Abbvie. K.C. has consulted for or received an honorarium from Puretech Health, Genentech, and Abbvie. K.C. has provisional patents, U.S. Patent Application. No. 15/625,934 and 62/935,035

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted October 20, 2020.
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Enteric viruses evoke broad host immune responses resembling bacterial microbiome
Dallari Simone, Heaney Thomas, Rosas-Villegas Adriana, Jessica A. Neil, Wong Serre-Yu, Judy J. Brown, Urbanek Kelly, Terence S. Dermody, Cadwell Ken
bioRxiv 2020.10.20.347286; doi: https://doi.org/10.1101/2020.10.20.347286
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Enteric viruses evoke broad host immune responses resembling bacterial microbiome
Dallari Simone, Heaney Thomas, Rosas-Villegas Adriana, Jessica A. Neil, Wong Serre-Yu, Judy J. Brown, Urbanek Kelly, Terence S. Dermody, Cadwell Ken
bioRxiv 2020.10.20.347286; doi: https://doi.org/10.1101/2020.10.20.347286

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