NR AWIS
AU Laude,H.
TI Diversity and complexity of natural ruminant prions
QU International Conference - Prion 2006: Strategies, advances and trends towards protection of society - 3.10.-6.10.2006, Torino, Italy, Lingotto Conference Centre - Oral sessions ORAL-12
PT Konferenz-Vortrag
AB
Scrapie in small ruminant is the most common natural prion disease. Earlier studies in our laboratory have shown that the use of transgenic mice expressing ovine PrPc (VRQ allele) greatly facilitates the sheep-to-mouse transmission of field isolates compared to conventional mice, thus providing a valuable tool to investigate natural variation of scrapie agent. Within a large panel of isolates from various European countries that were inoculated to one such line (tg338), all were found to successfully transmit disease. A notable strain-specific variation was observed based on the molecular profile and brain distribution of PrPres, and on the survival time upon primary and subsequent transmission. The picture emerging is that the scrapie agent comprises not less than five major strain groups, including the Nor98-like group called atypical scrapie. No correlation could be evidenced between the strain phenotype identified in mice and the PrP genotype of the donor. Each group could be clearly differentiated from BSE agent from various sources, thus consolidating existing data obtained through biochemical typing.
One major group of isolates produced a quite complex pattern of transmission, notably accompanied by a shift in the PrPres molecular profile and leading to the individualisation of phenotypically distinct strains. Strikingly, this phenomenon occurred also in a situation of homotypic transmission. Data from further transmission experiments provided strong evidence that this natural scrapie source consists of a mixture of strains. Of particular interest, the preferential amplification of one specific component appeared to be controlled by the level of PrPc expression in the brain. Furthermore, these strain components exhibited markedly different tropisms for the nervous and lymphoid tissues, leading to the preferential propagation of one component depending on the inoculation route. Thus, copropagation of distinct strain components within a same individual might account for the reported clinico-pathological heterogeneity between scrapie cases in addition to Prnp polymorphism and strain variation. Altogether these findings point to further complexity in the relationship between molecular properties of PrPsc and prion disease phenotype, and are of possible relevance with the recent observations of co-occurrence of multiple PrPsc types in human TSE patients. Transmission to ovine and bovine PrP transgenic mice was also found useful to characterise the newly recognised bovine prions and to analyse their relationship with epizootic BSE agent.
AD Virologie Immunologie Moléculaires, INRA, 78350 Jouy -en-josas, France
SP englisch
PO Italien