Reovirus type 3 clone 9 increases interleukin-1alpha level in the brain of neonatal, but not adult, mice.
Reovirus Type 3 clone 9 (T3C9)-induced lethal encephalitis is age dependent. We examined the effects of T3C9 inoculated into neonatal and adult mice by intracerebral, intramuscular, or peroral routes and the effect of lipopolysaccharide (LPS) on IL-1alpha levels in the blood and the brain. In parallel, we measured mice survival to T3C9 challenge, primary replication, and growth in and spread to the brain. The results show that T3C9 infection increased IL-1alpha only in the brain of neonatal mice, whereas LPS enhanced IL-1alpha in the brain and in the blood in both neonatal and adult mice. In neonatal mice, a T3C9-induced IL-1alpha increase coincided with viral replication-induced nervous tissue injury and preceded death. Anti-IL-1alpha antibody partially protected neonatal mice against T3C9 peroral challenge, further suggesting that this cytokine is involved in the mechanisms leading to lethal encephalitis. In adult mice, T3C9 was not lethal and did not modify IL-1alpha 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 T3C9 replication between newborn and adult mice could account in part for the age-dependent susceptibility to T3C9-induced lethal encephalitis.
Derrien
M
M
Department of Microbiology and Molecular Genetics, Harvard Medical School, 200 Longwood Avenue, Boston, Massachusetts, 02115, USA. mderrien@mail.med.cornell.edu
Fields
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BN
D000284:Administration, Oral; D000818:Animals; D000831:Animals, Newborn / Q000821:virology*; D000911:Antibodies, Monoclonal; D001921:Brain / Q000187:drug effects / Q000821:virology*; D002460:Cell Line; D007273:Injections, Intramuscular; D007276:Injections, Intraventricular; D007375:Interleukin-1 / Q000276:immunology / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D012087:Reoviridae / Q000235:genetics* / Q000378:metabolism; D012088:Reoviridae Infections / Q000378:metabolism*; D013997:Time Factors
D000911:Antibodies, Monoclonal; D007375:Interleukin-1; D008070:Lipopolysaccharides