Letter | Published:

An enteric virus can replace the beneficial function of commensal bacteria

Nature volume 516, pages 9498 (04 December 2014) | Download Citation


Intestinal microbial communities have profound effects on host physiology1. Whereas the symbiotic contribution of commensal bacteria is well established, the role of eukaryotic viruses that are present in the gastrointestinal tract under homeostatic conditions is undefined2,3. Here we demonstrate that a common enteric RNA virus can replace the beneficial function of commensal bacteria in the intestine. Murine norovirus (MNV) infection of germ-free or antibiotic-treated mice restored intestinal morphology and lymphocyte function without inducing overt inflammation and disease. The presence of MNV also suppressed an expansion of group 2 innate lymphoid cells observed in the absence of bacteria, and induced transcriptional changes in the intestine associated with immune development and type I interferon (IFN) signalling. Consistent with this observation, the IFN-α receptor was essential for the ability of MNV to compensate for bacterial depletion. Importantly, MNV infection offset the deleterious effect of treatment with antibiotics in models of intestinal injury and pathogenic bacterial infection. These data indicate that eukaryotic viruses have the capacity to support intestinal homeostasis and shape mucosal immunity, similarly to commensal bacteria.

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Primary accessions

Gene Expression Omnibus

Referenced accessions

NCBI Reference Sequence

Data deposits

RNA-seq data have been deposited in the Gene Expression Omnibus under accession number GSE60163. The MNV.SKI capsid sequence has been deposited in the NCBI Reference Sequence database under accession number KM463105.


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We would like to thank S. Koralov and P. Loke for advice on the manuscript, E. Venturini for assistance with deep sequencing, S. Brown and Z. Tang for data analysis, L. Ciriboga for CD3 staining, the flow cytometry and histopathology cores (Cancer Center Support Grant, P30CA016087) for assistance with sample preparation and analyses, M. Alva and D. Littman for assistance with breeding and maintaining GF mice, and H. Moura Silva for sample collection for MNV isolation. This research was supported by National Institutes of Health grant R01 DK093668 (K.C.) and a New York University Whitehead Fellowship (K.C.), Vilcek Fellowship (E.K.) and Erwin Schrödinger Fellowship from the Austrian Science Foundation (E.K.).

Author information


  1. Kimmel Center for Biology and Medicine at the Skirball Institute, New York University School of Medicine, New York, New York 10016, USA

    • Elisabeth Kernbauer
    •  & Ken Cadwell
  2. Department of Microbiology, New York University School of Medicine, New York, New York 10016, USA

    • Elisabeth Kernbauer
    •  & Ken Cadwell
  3. New York Presbyterian Hospital, New York, New York 10065, USA

    • Yi Ding
  4. Department of Pathology, New York University School of Medicine, New York, New York 10016, USA

    • Yi Ding


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E.K. performed all the experiments, Y.D. analysed and scored histological sections, K.C. and E.K. designed the study and wrote the manuscript.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Ken Cadwell.

Extended data

Supplementary information

Excel files

  1. 1.

    Supplementary Information

    This file contains the RNAseq table. Sheet 1 and sheet 2 show the mRNA counts for GF (uni N = 3), GF+MNV (MNV, N = 4) and GF+conv (conv, N = 4) which are above the threshold cutoff and which have been ranked according to their p-value after edgeR analysis. In sheet 1, ranked genes in the comparison GF to GF+MNV are shown; in sheet 2, GF was compared to GF+conv. For each gene the log fold change (logFC), log counts per million (log CPM) as well as the false discovery rate (FDR, calculated with the Benjamini’s and Hochberg algorithm) are shown.

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