Commensal microbes and interferon-λ determine persistence of enteric murine norovirus infection

Megan T. Baldridge, Timothy J. Nice, Broc T. McCune, Christine C. Yokoyama, Amal Kambal, Michael Wheadon, Michael S. Diamond, Yulia Ivanova, Maxim Artyomov, Herbert W. Virgin

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189 Scopus citations

Abstract

The capacity of human norovirus (NoV), which causes >90%of global epidemic nonbacterial gastroenteritis, to infect a subset of people persistently may contribute to its spread. How such enteric viruses establish persistent infections is not well understood. We found that antibiotics prevented persistent murine norovirus (MNoV) infection, an effect that was reversed by replenishment of the bacterial microbiota. Antibiotics did not prevent tissue infection or affect systemic viral replication but acted specifically in the intestine. The receptor for the antiviral cytokine interferon-λ, Ifnlr1, as well as the transcription factors Stat1 and Irf3, were required for antibiotics to prevent viral persistence. Thus, the bacterial microbiome fosters enteric viral persistence in a manner counteracted by specific components of the innate immune system.

Original languageEnglish (US)
Pages (from-to)266-269
Number of pages4
JournalScience
Volume347
Issue number6219
DOIs
StatePublished - Jan 16 2015

ASJC Scopus subject areas

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    Baldridge, M. T., Nice, T. J., McCune, B. T., Yokoyama, C. C., Kambal, A., Wheadon, M., Diamond, M. S., Ivanova, Y., Artyomov, M., & Virgin, H. W. (2015). Commensal microbes and interferon-λ determine persistence of enteric murine norovirus infection. Science, 347(6219), 266-269. https://doi.org/10.1126/science.1258025