DIFFERENTIAL IMMUNE RECOGNITION OF LCMV NUCLEOPROTEIN AND GLYCOPROTEIN IN TRANSGENIC MICE EXPRESSING LCMV CDNA GENES

We have generated doubly transgenic (DT) mice that independently expre ss cDNA genes for the nucleocapsid protein (NP) and the surface glycop roteins (GP) of lymphocytic choriomeningitis Virus (LCMV). By RT-PCR, transcription of both transgenes was detected at low levels in brain a nd kidney but was not observed in the thymus, Additionally, transcript ion of the GP transgene was observed in the spleen. Following challeng e with exogenous LCMV, an anti-NP CTL response was induced in LCMV-inf ected DT mice, suggesting that nonresponsiveness to NP had not been es tablished. In contrast, LCMV-infected DT mice were nonresponsive to GP and failed to mount any CTL response against GP, either at Day 7 or D ay 30 postinfection or following expansion of splenocyte populations i n vitro. A significant number (33%) of adult DT mice survived intracer ebral infection with LCMV, suggesting that virus-induced immunopatholo gy in the central nervous system can be diminished by combined express ion of the transgenes whereas no protective effect was conferred on si ngly transgenic mice, expressing NP or GP alone, the DT mice therefore create a novel host genetic background for comparative studies of the anti-LCMV immune responses relative to parental C57BI/6 mice. (C) 199 7 Academic Press.