Age-dependent susceptibility to reovirus encephalitis in mice is influenced by maturation of the type-I interferon response

Abstract

BackgroundInfants and young children are particularly susceptible to viral encephalitis; however, the mechanisms are unknown. We determined the age-dependent contribution of innate and adaptive immune functions to reovirus-induced encephalitis in mice.MethodsNewborn wild-Type mice, 2-20 days of age, were inoculated with reovirus or diluent and monitored for mortality, weight gain, and viral load. Four-and fifteen-day-old IFNAR-/-and RAG2-/-mice were inoculated with reovirus and similarly monitored.ResultsWeight gain was impaired in mice inoculated with reovirus at 8 days of age or less. Clinical signs of encephalitis were detected in mice inoculated at 10 days of age or less. Mortality decreased when mice were inoculated after 6 days of age. Survival was ≤15% in wild type (WT), RAG2-/-, and IFNAR-/-mice inoculated at 4 days of age. All WT mice, 92% of RAG2-/-mice, and only 48% of IFNAR-/-mice survived following inoculation at 15 days of age.ConclusionsSusceptibility of mice to reovirus-induced disease decreases between 6 and 8 days of age. Enhanced reovirus virulence in IFNAR-/-mice relative to WT and RAG2-/-mice inoculated at 15 days of age suggests that maturation of the type-I interferon response contributes to age-related mortality following reovirus infection.