Polyclonal increase in certain IgG subclasses in mice persistently infected with the 87V strain of scrapie.

Eight different combinations of seven strains of scrapie agent and the three known Sinc genotypes of mice were screened for changes in the concentration of IgG in serum. A single radial immunodiffusion assay was used to measure IgG throughout the incubation period which in different models ranged from an average of 125 days to longer than the maximum observation period of about 600 days. The only major changes occurred with the 87V strain of scrapie injected intracerebrally (i.c.) or intraperitoneally (i.p.) into mouse strains of the Sinc genotype p7p7. IgG concentration reached 1.5 to 2.0 times the control values in i.c. infected mice, which developed clinical disease after 270 to 320 days and also in i.p. infected mice, which did not develop the disease within the 600-day observation period. At very high IgG concentration, the increase was polyclonal; it involved the IgG 1 subclass more than the others and was accompanied by an increased rate of IgG clearance from serum. It is suggested that some scrapie infections of mice (and sheep) may upset the control of IgG production. The underlying mechanism may involve cell-pathogen interactions which are common to all scrapie infections, but only lead to gross changes in IgG in some combinations of agent strain and host genotype.

Further studies on changes in immunoglobulin G in the sera and CSF of Herdwick sheep with natural and experimental scrapie.

Previous studies showed that the concentration of IgG in serum was increased in a high proportion of Herdwick sheep in the clinical stage of natural scrapie. The present paper reports similar findings in Herdwicks with experimental scrapie in which the clinical signs were different. Further studies of the natural disease showed increased concentrations of IgG in CSF due to passive filtration from serum and not to local antibody production in the CNS. Qualitative differences in serum IgG have also been found in natural scrapie, involving a shift in the major IgG isotype from IgG1 to IgG2. The significance of these changes is not known but the limited evidence available may indicate a progressive dysfunction in certain sub-populations of lymphocytes in sheep scrapie.

Genetic markers in Herdwick sheep: no correlation with succeptibility or resistance to experimental scrapie.

Genetic markers were studied in Herdwick sheep, bred at Compton, with special reference to genetically selected lines which differ in susceptibility or resistance to experimentally produced scrapie. There were no correlations between susceptibility to the disease and albumin, pre-albumin, esterase and haemoglobin phenotypes, and between reduced glutathione levels and alpha-mannosidase isoenzymes, the latter possibly representing a previously undescribed genetic marker in sheep.

Search for scrapie-specific RNA and attempts to detect an infectious DNA or RNA.

Preparations of in vivo labelled RNA from normal and scrapie infected mouse brains were fractionated by polyacrylamide gel electrophoresis. No appreciable differences were detected between the two preparations. The biological activity of preparations of RNA and DNA from scrapie brain was also examined. In each case the nucleic acid was obtained by one method envolving the use of phenol and one without phenol. Attempts were made to bind the nucleic acid to normal membrane by three different methods. In no instance was a single case of scrapie obtained by inoculating nucleic acid extracts from scrapie brain either alone or associated with normal membranes. It is concluded that a putative scrapie-specific nucleic acid must either be present in scrapie brain in such an unusual from that it is not extracted readily by methods suitable for the preparation of most virus nucleic acids; or, if it is extracted, that it has no detectable biological activity. In either case, the scrapie agent differs substantially in its properties from the plant viroids.

Transferrin polymorphism in Herdwick sheep.

The transferrin system in Herdwick sheep, bred at Compton, was investigated with special reference to the susceptibility of the flock to experimentally produced scrapie. No significant correlations were observed between susceptibility and transferrin phenotypes.