Interferon-λ cures persistent murine norovirus infection in the absence of adaptive immunity

Timothy J. Nice, Megan T. Baldridge, Broc T. McCune, Jason M. Norman, Helen M. Lazear, Maxim Artyomov, Michael S. Diamond, Herbert W. Virgin

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185 Scopus citations

Abstract

Norovirus gastroenteritis is amajor public health burden worldwide. Although fecal shedding is important for transmission of enteric viruses, little is known about the immune factors that restrict persistent enteric infection. We report here that although the cytokines interferon-α (IFN-α) and IFN-β prevented the systemic spread of murine norovirus (MNoV), only IFN-λcontrolled persistent enteric infection. Infection-dependent induction of IFN-λ was governed by the MNoV capsid protein and correlated with diminished enteric persistence. Treatment of established infection with IFN-λ cured mice in a manner requiring nonhematopoietic cell expression of the IFN-λ receptor, Ifnlr1, and independent of adaptive immunity. These results suggest the therapeutic potential of IFN-λ for curing virus infections in the gastrointestinal tract.

Original languageEnglish (US)
Pages (from-to)269-273
Number of pages5
JournalScience
Volume347
Issue number6219
DOIs
StatePublished - Jan 16 2015

ASJC Scopus subject areas

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    Nice, T. J., Baldridge, M. T., McCune, B. T., Norman, J. M., Lazear, H. M., Artyomov, M., Diamond, M. S., & Virgin, H. W. (2015). Interferon-λ cures persistent murine norovirus infection in the absence of adaptive immunity. Science, 347(6219), 269-273. https://doi.org/10.1126/science.1258100