Virus Infection, Genetic Mutations, and Prion Infection in Prion Protein Conversion

Conformational conversion of the cellular isoform of prion protein, PrP(C), into the abnormally folded, amyloidogenic isoform, PrP(Sc), is an underlying pathogenic mechanism in prion diseases. The diseases manifest as sporadic, hereditary, and acquired disorders. Etiological mechanisms driving the conversion of PrP(C) into PrP(Sc) are unknown in sporadic prion diseases, while prion infection and specific mutations in the PrP gene are known to cause the conversion of PrP(C) into PrP(Sc) in acquired and hereditary prion diseases, respectively. We recently reported that a neurotropic strain of influenza A virus (IAV) induced the conversion of PrP(C) into PrP(Sc) 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 PrP(C) into PrP(Sc) in different types of prion diseases, by presenting our findings of the IAV infection-induced conversion of PrP(C) into PrP(Sc) 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 PrP(C) to convert into PrP(Sc) after prion infection.