Multiple mechanisms contribute to impairment of type 1 interferon production during chronic lymphocytic choriomeningitis virus infection of mice.
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.
Lee
Lian Ni
LN
The Edward Jenner Institute for Vaccine Research, Compton, Berkshire, United Kingdom.
Burke
Shannon
S
Montoya
Maria
M
Borrow
Persephone
P
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
D007370:Interferon Type I; D051193:Toll-Like Receptors