Cell culture models of transmissible spongiform encephalopathies

Abstract

Although numerous attempts have been made duringthe last 30 years to generate cellular models of prioninfection, very few cell models were available untilrecently. A few cell lines allowed the multiplication ofa very small number of experimental prion strains. Aproject was initiated to compensate for the lack of acellular system permissive to the multiplication of naturalstrains of prions. Four models have been generated.They are all permissive to ovine prion multiplicationand each has distinct features that should help to studythe different aspects of prion pathogenesis. In addition,the strategy used to derive these models couldalso be used to generate cell models of human or bovineprion infection. The ongoing work includes studieson the effects of prion infection on neuron biology, onthe identification of permissive cells in the peripheralnervous system, on the interaction of prions with thetarget cells, on the deregulation of genes involved inglycosylation, on the identification of drugs with antiprionactivity and on the role of PrP polymorphisms inscrapie susceptibility.