Reovirus type 3 clone 9 increases interleukin-1α level in the brain of neonatal, but not adult, mice

Abstract

Reovirus Type 3 clone 9 (T3C9)-induced lethal encephalitis is age dependent. We examined the effects of T309 inoculated into neonatal and adult mice by intracerebral, intramuscular, or peroral routes and the effect of lipopolysaccharide (LPS) on IL-1α levels in the blood and the brain. In parallel, we measured mice survival to T309 challenge, primary replication, and growth in and spread to the brain. The results show that T309 infection increased IL-1α only in the brain of neonatal mice, whereas LPS enhanced IL- 1α in the brain and in the blood in both neonatal and adult mice. In neonatal mice, a T3C9-induced IL-1α increase coincided with viral replication-induced nervous tissue injury and preceded death. Anti-IL-1α antibody partially protected neonatal mice against T309 peroral challenge, further suggesting that this cytokine is involved in the mechanisms leading to lethal encephalitis. In adult mice, T309 was not lethal and did not modify IL-1α levels although it slowly replicated in nervous tissues when inoculated directly into the brain. Together, these results suggest that differences in nervous tissue response to T309 replication between newborn and adult mice could account in part for the age-dependent susceptibility to T3C9-induced lethal encephalitis.