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/beta-induced genes was monitored during the development of lymphocytic choriomeningitis (LCM) to assess whether a restricted influence of these antiviral cytokines could be found in the central nervous system (CNS). High levels of IFN-alpha (83 +/- 42 U/ml) were present in the blood of LCM virus-infected mice 3 days postinfection, whereas IFN-beta was 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 and only low levels of IFN-beta mRNA were detected in brains. In situ hybridization showed IFN-alpha mRNA-expressing cells in the marginal zones of the spleen and in the subcapsular sinus and outer cortex of cervical lymph nodes. The expression of 2',5'-oligoadenylate synthetase (2',5'-OAS) mRNA followed the expression of IFN-beta mRNA in the brain, whereas 2',5'-OAS mRNA in the periphery was associated with systemic IFN-alpha. The localization of IFN-alpha-expressing cells in the spleen and lymph nodes in proximity to T- and B-cell compartments is consistent with a role for these cytokines in immune regulation. Furthermore, the absence of IFN-alpha and the relatively low level and delayed expression of IFN-beta in the brain suggest that the CNS is an especially vulnerable organ for virus replication. With certain strains of LCM virus, the absence of early antiviral IFN-alpha/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.
Sandberg
K
K
Department of Neuropharmacology, Scripps Research Institute, La Jolla, California.
Eloranta
M L
ML
Campbell
I L
IL
D015088:2',5'-Oligoadenylate Synthetase / Q000235:genetics; D000818:Animals; D006183:H-2 Antigens / Q000235:genetics; D016898:Interferon-alpha / Q000096:biosynthesis* / Q000235:genetics; D016899:Interferon-beta / Q000096:biosynthesis* / Q000235:genetics; D008198:Lymph Nodes / Q000378:metabolism; D008216:Lymphocytic Choriomeningitis / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D012333:RNA, Messenger / Q000032:analysis; D013154:Spleen / Q000378:metabolism
D006183:H-2 Antigens; D016898:Interferon-alpha; D012333:RNA, Messenger; D016899:Interferon-beta; D015088:2',5'-Oligoadenylate Synthetase