Dissociation between Transmissible Spongiform Encephalopathy (TSE) Infectivity and Proteinase K-Resistant PrPSc Levels in Peripheral Tissue from a Murine Transgenic Model of TSE Disease

Most current diagnostic tests for transmissible spongiform encephalopathies (TSE) rely on the presence of PK-resistant PrP(Sc) (PrP-res) in post-mortem tissues as indicative of TSE disease. However, a number of studies have highlighted a discrepancy between TSE infectivity and PrP-res levels in both natural and experimental cases of TSE disease. Previously we have shown high TSE infectivity levels in the brain tissue of mice that have a clinical TSE disease with associated vacuolar pathology but little or no PrP-res detectable. Here the levels of TSE infectivity and PrP-res within a peripheral tissue of this mouse model were investigated. Biochemical analysis identified low levels of PrP-res were present in the spleen tissue in comparison to levels observed in the spleen of mice infected with ME7 or 79A. However, upon sub-passage of brain and spleen tissue from clinically ill mice with little or no PrP-res detectable, similar short incubation periods to disease were observed, indicating that infectivity levels were similarly high in both tissues. Thus the discrepancy between PrP-res and TSE infectivity was also present in the peripheral tissues of this disease model. This result indicates that peripheral tissues can contain higher levels of infectivity given the correct combination of host species, PrP genotype and TSE agent. Therefore the assumption that levels of peripheral infectivity are lower than those in the central nervous system is not always correct and could have implications for current food safety regulations.