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

doi:10.1038/s41564-019-0416-7

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 journal › Letter › peer-review

86 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 gut^2,3. 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 language	English
Pages (from-to)	1120-1128
Number of pages	9
Journal	Nature microbiology
Volume	4
Issue number	7
DOIs	https://doi.org/10.1038/s41564-019-0416-7
State	Published - Jul 1 2019

Access to Document

10.1038/s41564-019-0416-7

Cite this

Ingle, H., Lee, S., Ai, T., Orvedahl, A., Rodgers, R., Zhao, G., Sullender, M., Peterson, S. T., Locke, M., Liu, T. C., Yokoyama, C. C., Sharp, B., Schultz-Cherry, S., Miner, J. J., & Baldridge, M. T. (2019). Viral complementation of immunodeficiency confers protection against enteric pathogens via interferon-λ. Nature microbiology, 4(7), 1120-1128. https://doi.org/10.1038/s41564-019-0416-7

@article{339ec19b584f460fb72a5b58d7e362ba,

title = "Viral complementation of immunodeficiency confers protection against enteric pathogens via interferon-λ",

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.",

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

note = "Publisher Copyright: {\textcopyright} 2019, The Author(s), under exclusive licence to Springer Nature Limited.",

year = "2019",

month = jul,

day = "1",

doi = "10.1038/s41564-019-0416-7",

language = "English",

volume = "4",

pages = "1120--1128",

journal = "Nature microbiology",

issn = "2058-5276",

number = "7",

}

Ingle, H, Lee, S, Ai, T, Orvedahl, A, Rodgers, R, Zhao, G, Sullender, M, Peterson, ST, Locke, M, Liu, TC , Yokoyama, CC, Sharp, B, Schultz-Cherry, S, Miner, JJ & Baldridge, MT 2019, 'Viral complementation of immunodeficiency confers protection against enteric pathogens via interferon-λ', Nature microbiology, vol. 4, no. 7, pp. 1120-1128. https://doi.org/10.1038/s41564-019-0416-7

TY - JOUR

T1 - Viral complementation of immunodeficiency confers protection against enteric pathogens via interferon-λ

AU - Ingle, Harshad

AU - Lee, Sanghyun

AU - Ai, Teresa

AU - Orvedahl, Anthony

AU - Rodgers, Rachel

AU - Zhao, Guoyan

AU - Sullender, Meagan

AU - Peterson, Stefan T.

AU - Locke, Marissa

AU - Liu, Ta Chiang

AU - Yokoyama, Christine C.

AU - Sharp, Bridgett

AU - Schultz-Cherry, Stacey

AU - Miner, Jonathan J.

AU - Baldridge, Megan T.

PY - 2019/7/1

Y1 - 2019/7/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85063719147&partnerID=8YFLogxK

U2 - 10.1038/s41564-019-0416-7

DO - 10.1038/s41564-019-0416-7

M3 - Letter

C2 - 30936486

AN - SCOPUS:85063719147

SN - 2058-5276

VL - 4

SP - 1120

EP - 1128

JO - Nature microbiology

JF - Nature microbiology

IS - 7

ER -

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

Abstract

Access to Document

Other files and links

Fingerprint

Cite this