title: Commensal microbes and interferon-λ determine persistence of enteric murine norovirus infection.
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.
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: 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: 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: Christine C
authors.initials: CC
authors.lastname: Yokoyama
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Amal
authors.initials: A
authors.lastname: Kambal
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Wheadon
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA. Departments of Medicine and 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.
authors.forename: Yulia
authors.initials: Y
authors.lastname: Ivanova
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. virgin@wustl.edu.
authors.forename: Herbert W
authors.initials: HW
authors.lastname: Virgin
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D017250:Caliciviridae Infections / Q000188:drug therapy / Q000276:immunology / Q000382:microbiology / Q000821:virology*; D016207:Cytokines / Q000502:physiology*; D005260:Female; D005759:Gastroenteritis / Q000188:drug therapy / Q000276:immunology / Q000382:microbiology / Q000821:virology*; D007422:Intestines / Q000382:microbiology* / Q000821:virology; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D064307:Microbiota / Q000187:drug effects; D029322:Norovirus / Q000276:immunology / Q000502:physiology*; D018121:Receptors, Cytokine / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013559:Symbiosis; D019562:Viral Load; D014779:Virus Replication; D017201:Virus Shedding; D007378:Interleukins; D000095022:Interferon Lambda
chemical_list: D000900:Anti-Bacterial Agents; D016207:Cytokines; D018121:Receptors, Cytokine; C511668:interferon-lambda protein, mouse; D007378:Interleukins; D000095022:Interferon Lambda