@article{6186f268b6b54423865881afa504b5a5,
title = "Enteric viruses evoke broad host immune responses resembling those elicited by the bacterial microbiome",
abstract = "The 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. Infections with most of these viruses were asymptomatic in 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 persisted. Comparison with a dataset derived from analogous bacterial mono-association in mice identified bacterial species that evoke an immune response comparable with 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.",
keywords = "enteric virome, host-virome relationship, regulation of the enteric immune system, virome, virus",
author = "Simone Dallari and Thomas Heaney and Adriana Rosas-Villegas and Neil, {Jessica A.} and Wong, {Serre Yu} and Brown, {Judy J.} and Kelly Urbanek and Christin Herrmann and Depledge, {Daniel P.} and Dermody, {Terence S.} and Ken Cadwell",
note = "Funding Information: We wish to thank Drs. Julie Pfeiffer (UT Southwestern), Jason G. Smith (University of Washington), David Pintel (University of Missouri), Peter Tattersall (Yale University), Harry B Greenberg (Stanford University), and Kathy McCoy (University of Calgary) for sharing reagents and culturing techniques; Dr. P'ng Loke (NIH) for comments on the manuscript, NYU Grossman School of Medicine Flow Cytometry and Cell Sorting, Microscopy, Genome Technology, and Histology Cores for use of their instruments and technical assistance (supported by National Institutes of Health [NIH] grants P31CA016087, S10OD01058, and S10OD018338); and Margie Alva, Juan Carrasquillo, and Beatriz Delgado for assistance with gnotobiotics. This research was supported by NIH grants DK093668 (K.C.), AI121244 (K.C.), HL123340 (K.C.), AI130945 (K.C.), AI140754 (K.C.), DK108562 (J.J.B.), HL007751 (J.J.B.), AI038296 (T.S.D.), and DK098435 (T.S.D.), as well as by a pilot award from the NYU Cancer Center grant P30CA016087 (K.C.). Additional support was provided by the Faculty Scholar grant from the Howard Hughes Medical Institute (K.C.), Crohn's & Colitis Foundation (K.C.), Merieux Institute (K.C.), Kenneth Rainin Foundation (K.C.), Judith & Stewart Colton Center of Autoimmunity (K.C.), and the Heinz Endowments (T.S.D.). K.C. is a Burroughs Wellcome Fund Investigator in the Pathogenesis of Infectious Diseases. Figure S2A and graphical abstract were created using BioRender.com. S.D. and K.C. conceived the study and designed the experiments. S.D. performed, analyzed, and interpreted all the experiments. T.H. and A.R.-V. helped perform viral inoculation experiments. J.A.N. helped design and interpret data regarding MNV. S.-Y.W. prepared the minimal defined flora. J.J.B. K.U. and T.S.D. provided T1L virus and helped design T1L detection method. C.H. and D.P.D. sequenced the MuAstV stock. K.C. oversaw the analysis and interpretation of all experiments described. S.D. and K.C. wrote the manuscript with inputs from all authors. K.C. has received research support from Pfizer, Takeda, Pacific Biosciences, and Abbvie. K.C. has also consulted for or received an honorarium from Puretech Health, Genentech, and Abbvie. K.C. holds U.S. patent 10,722,600 and provisional patent 62/935,035. Funding Information: We wish to thank Drs. Julie Pfeiffer (UT Southwestern), Jason G. Smith (University of Washington), David Pintel (University of Missouri), Peter Tattersall (Yale University), Harry B Greenberg (Stanford University), and Kathy McCoy (University of Calgary) for sharing reagents and culturing techniques; Dr. P{\textquoteright}ng Loke (NIH) for comments on the manuscript, NYU Grossman School of Medicine Flow Cytometry and Cell Sorting, Microscopy, Genome Technology, and Histology Cores for use of their instruments and technical assistance (supported by National Institutes of Health [ NIH ] grants P31CA016087 , S10OD01058 , and S10OD018338 ); and Margie Alva, Juan Carrasquillo, and Beatriz Delgado for assistance with gnotobiotics. This research was supported by NIH grants DK093668 (K.C.), AI121244 (K.C.), HL123340 (K.C.), AI130945 (K.C.), AI140754 (K.C.), DK108562 (J.J.B.), HL007751 (J.J.B.), AI038296 (T.S.D.), and DK098435 (T.S.D.), as well as by a pilot award from the NYU Cancer Center grant P30CA016087 (K.C.). Additional support was provided by the Faculty Scholar grant from the Howard Hughes Medical Institute (K.C.), Crohn{\textquoteright}s & Colitis Foundation (K.C.), Merieux Institute (K.C.), Kenneth Rainin Foundation (K.C.), Judith & Stewart Colton Center of Autoimmunity (K.C.), and the Heinz Endowments (T.S.D.). K.C. is a Burroughs Wellcome Fund Investigator in the Pathogenesis of Infectious Diseases. Figure S2 A and graphical abstract were created using BioRender.com . Publisher Copyright: {\textcopyright} 2021 Elsevier Inc.",
year = "2021",
month = jun,
day = "9",
doi = "10.1016/j.chom.2021.03.015",
language = "English",
volume = "29",
pages = "1014--1029.e8",
journal = "Cell Host and Microbe",
issn = "1931-3128",
publisher = "Cell Press",
number = "6",
}