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

doi:10.1126/science.1258100

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

Research output: Contribution to journal › Article › peer-review

276 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 language	English (US)
Pages (from-to)	269-273
Number of pages	5
Journal	Science
Volume	347
Issue number	6219
DOIs	https://doi.org/10.1126/science.1258100
State	Published - Jan 16 2015
Externally published	Yes

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title = "Interferon-λ cures persistent murine norovirus infection in the absence of adaptive immunity",

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.",

author = "Nice, {Timothy J.} and Baldridge, {Megan T.} and McCune, {Broc T.} and Norman, {Jason M.} and Lazear, {Helen M.} and Maxim Artyomov and Diamond, {Michael S.} and Virgin, {Herbert W.}",

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AU - Nice, Timothy J.

AU - Baldridge, Megan T.

AU - McCune, Broc T.

AU - Norman, Jason M.

AU - Lazear, Helen M.

AU - Artyomov, Maxim

AU - Diamond, Michael S.

AU - Virgin, Herbert W.

PY - 2015/1/16

Y1 - 2015/1/16

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AB - 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.

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

Abstract

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