Differential Immune Recognition of LCMV Nucleoprotein and Glycoprotein in Transgenic Mice Expressing LCMV cDNA Genes

AbstractWe have generated doubly transgenic (DT) mice that independently express cDNA genes for the nucleocapsid protein (NP) and the surface glycoproteins (GP) of lymphocytic choriomeningitis virus (LCMV). By RT-PCR, transcription of both transgenes was detected at low levels in brain and kidney but was not observed in the thymus. Additionally, transcription of the GP transgene was observed in the spleen. Following challenge with exogenous LCMV, an anti-NP CTL response was induced in LCMV-infected DT mice, suggesting that nonresponsiveness to NP had not been established. In contrast, LCMV-infected DT mice were nonresponsive to GP and failed to mount any CTL response against GP, either at Day 7 or Day 30 postinfection or following expansion of splenocyte populationsin vitro.A significant number (33%) of adult DT mice survived intracerebral infection with LCMV, suggesting that virus-induced immunopathology in the central nervous system can be diminished by combined expression of the transgenes whereas no protective effect was conferred on singly 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 C57Bl/6 mice

Human PKR Transfected into Murine Cells Stimulates Expression of Genes under Control of the HIV1 or HTLV-I LTR

AbstractWe have analyzed the effect of transfection into murine NIH/3T3 cells of the human dsRNA-activated kinase PKR on the expression of the β-galactosidase reporter gene, placed under control of the HIV1 or the HTLV-I LTR. β-Galactosidase expression is stimulated when the reporter plasmids are cotransfected with wild-type PKR but inhibited when cotransfected with a catalytically inactive mutant PKR. In the case of HIV1, β-galactosidase expression was not stimulated when cotransfection was carried out with PKR harboring mutations in the dsRNA binding domains, indicating that stimulation depends on the classical mode of PKR activation through dsRNA binding. In contrast, the dsRNA binding mutants of PKR could still partially stimulate β-galactosidase expression from the HTLV-I LTR, suggesting that PKR activation in this case may involve different/additional mechanisms. These results show that, in addition to the known down-regulation of protein synthesis through eIF2 phosphorylation, PKR can also positively stimulate gene expressionin vivo,most probably through phosphorylation of a substrate distinct from eIF2

A systematic and population genetic approach to the rabies problem in the yellow mongoose (Cynictis penicillata)

This paper reviews recent studies on the biology, systematics and population genetics of yellow mongoose populations in terms of possible implications for the epidemiology of rabies. Based on parallel studies, the existence of three distinct subspecies of yellow mongoose may have a direct bearing on rabies epidemiology; at least subspecific affiliation should be considered as a factor to be controlled for in rabies studies of the species. A direct correlation was found to exist between population genetics, social structure (and vagility) and aspects of the epidemiology of rabies in the yellow mongoose. The high frequency of enzyme polymorphisms restricted to single populations can be understood in terms of the well developed social structure and low vagility of yellow mongooses, which in turn explains the phenomenon of rabies outbreaks being restricted to highly localized foci which may flare up over a period of several years. Further research is required to establish whether predictable population genetic differences exist between high and low rabies-prone populations.The articles have been scanned in colour with a HP Scanjet 5590; 600dpi. Adobe Acrobat XI Pro was used to OCR the text and also for the merging and conversion to the final presentation PDF-format.FRD.mn201