RESUMO
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.
Assuntos
Síndrome de Creutzfeldt-Jakob/genética , Doença de Gerstmann-Straussler-Scheinker/genética , Influenza Humana/genética , Insônia Familiar Fatal/genética , Proteínas PrPC/genética , Proteínas PrPSc/genética , Proteínas Priônicas/genética , Animais , Linhagem Celular Tumoral , Síndrome de Creutzfeldt-Jakob/metabolismo , Síndrome de Creutzfeldt-Jakob/patologia , Síndrome de Creutzfeldt-Jakob/virologia , Doença de Gerstmann-Straussler-Scheinker/metabolismo , Doença de Gerstmann-Straussler-Scheinker/patologia , Doença de Gerstmann-Straussler-Scheinker/virologia , Humanos , Vírus da Influenza A/genética , Vírus da Influenza A/crescimento & desenvolvimento , Vírus da Influenza A/patogenicidade , Influenza Humana/metabolismo , Influenza Humana/patologia , Influenza Humana/virologia , Insônia Familiar Fatal/metabolismo , Insônia Familiar Fatal/patologia , Insônia Familiar Fatal/virologia , Camundongos , Camundongos Transgênicos , Mutação , Neurônios/metabolismo , Neurônios/patologia , Neurônios/virologia , Proteínas PrPC/química , Proteínas PrPC/metabolismo , Proteínas PrPSc/química , Proteínas PrPSc/metabolismo , Proteínas Priônicas/química , Proteínas Priônicas/metabolismo , Conformação Proteica , Genética Reversa/métodosRESUMO
On the basis of clinical picture of the disease, data of CT, MRT, psychological study, original laboratory investigation aimed at indication of changes in transposed neuroglia cells induced by the causal agent of subacute spongious transmissible encephalopathies, the diagnosis of patient K., 49 years old, was considered to be: syndrome of Gertsmann-Sträussler [correction of Herstmann Streussler]. Duration of the disease was 2 years. The case was sporadic. The history of the problem, modern views on etiology, pathogenesis of preventive measures are presented.