title: Interferon-λ cures persistent murine norovirus infection in the absence of adaptive immunity.
abstract: Norovirus gastroenteritis is a major 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-λ controlled 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.
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Nice
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Megan T
authors.initials: MT
authors.lastname: Baldridge
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Broc T
authors.initials: BT
authors.lastname: McCune
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Jason M
authors.initials: JM
authors.lastname: Norman
authors.affiliation: Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Helen M
authors.initials: HM
authors.lastname: Lazear
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Maxim
authors.initials: M
authors.lastname: Artyomov
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA. Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA. Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Diamond
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA. virgin@wustl.edu.
authors.forename: Herbert W
authors.initials: HW
authors.lastname: Virgin
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D017250:Caliciviridae Infections / Q000188:drug therapy* / Q000276:immunology* / Q000821:virology; D036022:Capsid Proteins / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology* / Q000627:therapeutic use*; D005243:Feces / Q000821:virology; D005759:Gastroenteritis / Q000188:drug therapy / Q000276:immunology* / Q000821:virology; D007113:Immunity, Innate; D016898:Interferon-alpha / Q000096:biosynthesis / Q000276:immunology; D016899:Interferon-beta / Q000096:biosynthesis / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D029322:Norovirus / Q000276:immunology* / Q000502:physiology*; D014779:Virus Replication; D017201:Virus Shedding; D007378:Interleukins; D000095022:Interferon Lambda
chemical_list: D036022:Capsid Proteins; D016207:Cytokines; D016898:Interferon-alpha; D016899:Interferon-beta; C511668:interferon-lambda protein, mouse; D007378:Interleukins; D000095022:Interferon Lambda