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, but 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 to 20 days of age, were inoculated with reovirus or diluent and monitored for mortality, weight gain, and viral load. Four and 15-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 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 innate immune system contributes to age-related mortality following reovirus infection.