RETRACTED ARTICLE: Neurotropic influenza A virus infection causes prion protein misfolding into infectious prions in neuroblastoma cells
Hideyuki Hara, Junji Chida, Keiji Uchiyama, Agriani Dini Pasiana, Etsuhisa Takahashi, Hiroshi Kido, Suehiro Sakaguchi
Abstract
Abstract Misfolding of the cellular prion protein, PrP C , into the amyloidogenic isoform, PrP Sc , which forms infectious protein aggregates, the so-called prions, is a key pathogenic event in prion diseases. No pathogens other than prions have been identified to induce misfolding of PrP C into PrP Sc and propagate infectious prions in infected cells. Here, we found that infection with a neurotropic influenza A virus strain (IAV/WSN) caused misfolding of PrP C into PrP Sc and generated infectious prions in mouse neuroblastoma cells through a hit-and-run mechanism. The structural and biochemical characteristics of IAV/WSN-induced PrP Sc were different from those of RML and 22L laboratory prions-evoked PrP Sc , and the pathogenicity of IAV/WSN-induced prions were also different from that of RML and 22L prions, suggesting IAV/WSN-specific formation of PrP Sc and infectious prions. Our current results may open a new avenue for the role of viral infection in misfolding of PrP C into PrP Sc and formation of infectious prions.