ABSTRACT
Conformational conversion of the cellular isoform of prion protein, PrPC, into the abnormally folded, amyloidogenic isoform, PrPSc, is an underlying pathogenic mechanism in prion diseases. The diseases manifest as sporadic, hereditary, and acquired disorders. Etiological mechanisms driving the conversion of PrPC into PrPSc are unknown in sporadic prion diseases, while prion infection and specific mutations in the PrP gene are known to cause the conversion of PrPC into PrPSc in acquired and hereditary prion diseases, respectively. We recently reported that a neurotropic strain of influenza A virus (IAV) induced the conversion of PrPC into PrPSc as well as formation of infectious prions in mouse neuroblastoma cells after infection, suggesting the causative role of the neuronal infection of IAV in sporadic prion diseases. Here, we discuss the conversion mechanism of PrPC into PrPSc in different types of prion diseases, by presenting our findings of the IAV infection-induced conversion of PrPC into PrPSc and by reviewing the so far reported transgenic animal models of hereditary prion diseases and the reverse genetic studies, which have revealed the structure-function relationship for PrPC to convert into PrPSc after prion infection.
Subject(s)
Creutzfeldt-Jakob Syndrome/genetics , Gerstmann-Straussler-Scheinker Disease/genetics , Influenza, Human/genetics , Insomnia, Fatal Familial/genetics , PrPC Proteins/genetics , PrPSc Proteins/genetics , Prion Proteins/genetics , Animals , Cell Line, Tumor , Creutzfeldt-Jakob Syndrome/metabolism , Creutzfeldt-Jakob Syndrome/pathology , Creutzfeldt-Jakob Syndrome/virology , Gerstmann-Straussler-Scheinker Disease/metabolism , Gerstmann-Straussler-Scheinker Disease/pathology , Gerstmann-Straussler-Scheinker Disease/virology , Humans , Influenza A virus/genetics , Influenza A virus/growth & development , Influenza A virus/pathogenicity , Influenza, Human/metabolism , Influenza, Human/pathology , Influenza, Human/virology , Insomnia, Fatal Familial/metabolism , Insomnia, Fatal Familial/pathology , Insomnia, Fatal Familial/virology , Mice , Mice, Transgenic , Mutation , Neurons/metabolism , Neurons/pathology , Neurons/virology , PrPC Proteins/chemistry , PrPC Proteins/metabolism , PrPSc Proteins/chemistry , PrPSc Proteins/metabolism , Prion Proteins/chemistry , Prion Proteins/metabolism , Protein Conformation , Reverse Genetics/methodsABSTRACT
The prion diseases or transmissible spongiform encephalopathies (TSE) constitute a group of hereditary or acquired neurodegenerative disorders. The Authors evaluate the etiopathogenetic background, the clinical features and the current concerns with special attention to bovine spongiform encephalopathy and new variant Creutzfeldt Jacob disease.
