title: Blockade of interferon Beta, but not interferon alpha, signaling controls persistent viral infection.
abstract: Although type I interferon (IFN-I) is thought to be beneficial against microbial infections, persistent viral infections are characterized by high interferon signatures suggesting that IFN-I signaling may promote disease pathogenesis. During persistent lymphocytic choriomeningitis virus (LCMV) infection, IFNα and IFNβ are highly induced early after infection, and blocking IFN-I receptor (IFNAR) signaling promotes virus clearance. We assessed the specific roles of IFNβ versus IFNα in controlling LCMV infection. While blockade of IFNβ alone does not alter early viral dissemination, it is important in determining lymphoid structure, lymphocyte migration, and anti-viral T cell responses that lead to accelerated virus clearance, approximating what occurs during attenuation of IFNAR signaling. Comparatively, blockade of IFNα was not associated with improved viral control, but with early dissemination of virus. Thus, despite their use of the same receptor, IFNβ and IFNα have unique and distinguishable biologic functions, with IFNβ being mainly responsible for promoting viral persistence.
authors.affiliation: Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Cherie T
authors.initials: CT
authors.lastname: Ng
authors.affiliation: Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Brian M
authors.initials: BM
authors.lastname: Sullivan
authors.affiliation: Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: John R
authors.initials: JR
authors.lastname: Teijaro
authors.affiliation: Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Lee
authors.affiliation: Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Megan
authors.initials: M
authors.lastname: Welch
authors.affiliation: Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Rice
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Kathleen C F
authors.initials: KC
authors.lastname: Sheehan
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Robert D
authors.initials: RD
authors.lastname: Schreiber
authors.affiliation: Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA. Electronic address: mbaobo@scripps.edu.
authors.forename: Michael B A
authors.initials: MB
authors.lastname: Oldstone
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D016898:Interferon-alpha / Q000378:metabolism*; D016899:Interferon-beta / Q000378:metabolism*; D008216:Lymphocytic Choriomeningitis / Q000276:immunology* / Q000821:virology*; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology*; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015398:Signal Transduction
chemical_list: D016898:Interferon-alpha; D016899:Interferon-beta