EXPRESSION OF ALPHA BETA INTERFERONS (IFN-ALPHA/BETA) AND THEIR RELATIONSHIP TO IFN-ALPHA/BETA-INDUCED GENES IN LYMPHOCYTIC CHORIOMENINGITIS/

Expression of alpha interferon (IFN-alpha), IFN-beta-, and IFN-alpha/b eta-induced genes was monitored during the development of lymphocytic choriomeningitis (LCM) to assess whether a restricted influence of the se antiviral cytokines could be found in the central nervous system (C NS). High levels of IFN-alpha (83 +/- 42 U/ml) were present int he blo od of LCM virus-infected mice 3 days postinfection, whereas IFN-beta w as not detected (<1.0 U/ml) at any time point. Spleens contained high levels of IFN-alpha and IFN-beta mRNAs at days 1 and 3 postinfection, whereas no IFN-alpha mRNA nad only low levels of IFN-beta mRNA were de tected in brains. In situ hybridization showed IFN-alpha mRNA-expressi ng cells in the marginal zones of the spleen and in the subcapsular si nus and outer cortex of cervical lymph nodes. The expression of 2',5'- oligoadenylate synthetase (2',5'-OAS mRNA followed the expression of I FN-beta mRNA in the brain, whereas 2',5'-OAS mRNA in the periphery was associated with systemic IFN-alpha. The localization of IFN-alpha-exp ressing cells in the spleen and lymph nodes in proximity to T-and B-ce ll compartments is consistent with a role for these cytokines in immun e regulation. Furthermore, the absence of IFN-alpha and the relatively low level and delayed expression of IFN-beta in the brain suggest tha t the CNS is an especially vulnerable organ for virus replication. Wit h certain strains of LCM virus, the absence of early antiviral IFN-alp ha/beta activity and preferential virus growth in the brain might lead to targeted T-cell inflammation of the CNS, resulting in death of the animal.