Viral complementation of immunodeficiency confers protection against enteric pathogens via interferon-λ

Harshad Ingle, Sanghyun Lee, Teresa Ai, Anthony Orvedahl, Rachel Rodgers, Guoyan Zhao, Meagan Sullender, Stefan T. Peterson, Marissa Locke, Ta Chiang Liu, Christine C. Yokoyama, Bridgett Sharp, Stacey Schultz-Cherry, Jonathan J. Miner, Megan T. Baldridge

Research output: Contribution to journalLetterpeer-review

42 Scopus citations

Abstract

Commensal microbes profoundly impact host immunity to enteric viral infections1. We have shown that the bacterial microbiota and host antiviral cytokine interferon-λ (IFN-λ) determine the persistence of murine norovirus in the gut2,3. However, the effects of the virome in modulating enteric infections remain unexplored. Here, we report that murine astrovirus can complement primary immunodeficiency to protect against murine norovirus and rotavirus infections. Protection against infection was horizontally transferable between immunocompromised mouse strains by co-housing and fecal transplantation. Furthermore, protection against enteric pathogens corresponded with the presence of a specific strain of murine astrovirus in the gut, and this complementation of immunodeficiency required IFN-λ signalling in gut epithelial cells. Our study demonstrates that elements of the virome can protect against enteric pathogens in an immunodeficient host.

Original languageEnglish
Pages (from-to)1120-1128
Number of pages9
JournalNature microbiology
Volume4
Issue number7
DOIs
StatePublished - Jul 1 2019

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