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Strain diversity in transmissible spongiform encephalitis of ruminants : concerns, facts and prospects

Inra Prod. Anim., 2004, Numéro hors série, 13-20


1 INRA, Pathologie Infectieuse et Immunité, F-37380 Nouzilly

2 INRA, Virologie Immunologie Moléculaires, F-78350 Jouy-en-Josas


A hallmark of Transmissible SpongiformEncephalopathies (TSE) or prion diseases is the accumulationin nervous tissues of an abnormally foldedform of the host protein PrPc. This misfolded isoform(PrPsc) is assumed to be responsible for the observedneurodegenerative disorders, and is the only componentspecifically associated with prion infectivity yetidentified. The most widely held view is that prions propagateepigenetically, through the conversion of PrPcinto PrPsc. A phenomenon at the heart of the researchon prion diseases is the existence of phenotypicalvariants, or strains. Prion strains can be differentiatedon a biological basis, since different strains induce differentanotomo-pathological manifestations upon propagationinto the same host, and on a biochemicalbasis, i.e. the molecular profile of PrPsc accumulatingin the brain of the diseased individuals. However, theprecise biological and molecular mechanisms underlyingsuch diversity and the evolution dynamics that itimplies, remain to be learned. Investigating prionstrain variation in naturally infected species, such assheep and humans, is a highly demanding task, albeitcrucial for a better knowledge of the epidemiology ofthese diseases, their control on the field, and the protectionof human health. Research carried out by INRAlaboratories is aimed at documenting TSE strain diversityin ruminants through the typing of natural sheepscrapie isolates, and at improving our understanding ofthis phenomenon. One way to achieve these objectivesis to develop faster and more reliable typing methods,including through the development of transgenic miceexhibiting a higher susceptibility to transmsission overconventional mice.

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