The first non-prion pathogen identified: neurotropic influenza virus

The cellular isoform of prion protein, designated PrP(C), is a membrane glycoprotein expressed most abundantly in the brain, particularly by neurons, and its conformational conversion into the abnormally folded, amyloidogenic isoform, PrP(Sc), is an underlying mechanism in the pathogenesis of prion diseases, a group of neurodegenerative disorders in humans and animals. Most cases of these diseases are sporadic and their aetiologies are unknown. We recently found that a neurotropic strain of influenza A virus (IAV/WSN) caused the conversion of PrP(C) into PrP(Sc) and the subsequent formation of infectious prions in mouse neuroblastoma cells after infection. These results show that IAV/WSN is the first non-prion pathogen capable of inducing the conversion of PrP(C) into PrP(Sc) and propagating infectious prions in cultured neuronal cells, and also provide the intriguing possibility that IAV infection in neurons might be a cause of or be associated with sporadic prion diseases. Here, we present our findings of the IAV/WSN-induced conversion of PrP(C) into PrP(Sc) and subsequent propagation of infectious prions, and also discuss the biological significance of the conversion of PrP(C) into PrP(Sc) in virus infections.