title: Multiple mechanisms contribute to impairment of type 1 interferon production during chronic lymphocytic choriomeningitis virus infection of mice.
abstract: Type 1 IFNs, innate cytokines with important effector and immunomodulatory properties, are rapidly induced in the acute phase of many virus infections; however, this is generally a transient response that is not sustained during virus persistence. To gain insight into mechanisms that can contribute to down-regulation of type 1 IFN production during virus persistence, we analyzed type 1 IFN production during acute and chronic lymphocytic choriomeningitis virus (LCMV) infection. High-level type 1 IFN production was transiently up-regulated in cells including plasmacytoid and conventional dendritic cells (DCs) following LCMV infection of mice, but LCMV persistence was associated with only low-level type 1 IFN production. Nonetheless, chronically infected mice were able to up-regulate type 1 IFN production in response to TLR3, 7, and 9 ligands, albeit less efficiently than uninfected mice. Splenic DC numbers in mice chronically infected with LCMV were decreased, and the remaining cells exhibited a reduced response to TLR stimulation. LCMV-infected cell lines efficiently up-regulated type 1 IFN production following TLR ligation and infection with a DNA virus, but exhibited a defect in type 1 IFN induction following infection with Sendai, an RNA virus. This block in type 1 IFN production by infected cells, together with abnormalities in DC numbers and functions, likely contribute to the low-level type 1 IFN production in mice chronically infected with LCMV. Impairment of type 1 IFN production may both promote virus persistence and impact on host immunocompetence. Understanding the mechanisms involved may assist in development of strategies for control of virus persistence and superinfection.
authors.affiliation: The Edward Jenner Institute for Vaccine Research, Compton, Berkshire, United Kingdom.
authors.forename: Lian Ni
authors.initials: LN
authors.lastname: Lee
authors.forename: Shannon
authors.initials: S
authors.lastname: Burke
authors.forename: Maria
authors.initials: M
authors.lastname: Montoya
authors.forename: Persephone
authors.initials: P
authors.lastname: Borrow
mesh_terms: D000818:Animals; D004267:DNA Viruses / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology; D005786:Gene Expression Regulation / Q000276:immunology; D007370:Interferon Type I / Q000096:biosynthesis*; D008216:Lymphocytic Choriomeningitis / Q000276:immunology; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology; D051379:Mice; D010950:Plasma Cells / Q000276:immunology; D012328:RNA Viruses / Q000276:immunology; D013154:Spleen / Q000166:cytology; D051193:Toll-Like Receptors / Q000276:immunology
chemical_list: D007370:Interferon Type I; D051193:Toll-Like Receptors