Enteric viruses evoke broad host immune responses resembling those elicited by the bacterial microbiome

Cell Host Microbe. 2021 Jun 9;29(6):1014-1029.e8. doi: 10.1016/j.chom.2021.03.015. Epub 2021 Apr 23.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Asymptomatic Infections
  • Bacteria / metabolism
  • Cytokines / metabolism*
  • Enterovirus Infections / immunology*
  • Gastrointestinal Microbiome*
  • Gene Expression Regulation, Bacterial
  • Germ-Free Life
  • Host Microbial Interactions
  • Immunity*
  • Intestines / immunology
  • Intestines / virology
  • Mice
  • Mice, Inbred C57BL
  • Symbiosis
  • T-Lymphocytes / metabolism
  • Transcriptome*
  • Virome*
  • Viruses / immunology*


  • Cytokines