Neurotropic influenza A virus infection causes prion protein misfolding into infectious prions in neuroblastoma cells

Abstract Misfolding of the cellular prion protein, PrPC, into the amyloidogenic isoform, PrPSc, 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 PrPC into PrPSc an...

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Autores principales: Hideyuki Hara, Junji Chida, Keiji Uchiyama, Agriani Dini Pasiana, Etsuhisa Takahashi, Hiroshi Kido, Suehiro Sakaguchi
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Publicado: Nature Portfolio 2021
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Acceso en línea:https://doaj.org/article/54c57a68787c4beb8f8d7706db3b0d5c
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spelling oai:doaj.org-article:54c57a68787c4beb8f8d7706db3b0d5c2021-12-02T17:15:36ZNeurotropic influenza A virus infection causes prion protein misfolding into infectious prions in neuroblastoma cells10.1038/s41598-021-89586-62045-2322https://doaj.org/article/54c57a68787c4beb8f8d7706db3b0d5c2021-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-89586-6https://doaj.org/toc/2045-2322Abstract Misfolding of the cellular prion protein, PrPC, into the amyloidogenic isoform, PrPSc, 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 PrPC into PrPSc and propagate infectious prions in infected cells. Here, we found that infection with a neurotropic influenza A virus strain (IAV/WSN) caused misfolding of PrPC into PrPSc and generated infectious prions in mouse neuroblastoma cells through a hit-and-run mechanism. The structural and biochemical characteristics of IAV/WSN-induced PrPSc were different from those of RML and 22L laboratory prions-evoked PrPSc, and the pathogenicity of IAV/WSN-induced prions were also different from that of RML and 22L prions, suggesting IAV/WSN-specific formation of PrPSc and infectious prions. Our current results may open a new avenue for the role of viral infection in misfolding of PrPC into PrPSc and formation of infectious prions.Hideyuki HaraJunji ChidaKeiji UchiyamaAgriani Dini PasianaEtsuhisa TakahashiHiroshi KidoSuehiro SakaguchiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Hideyuki Hara
Junji Chida
Keiji Uchiyama
Agriani Dini Pasiana
Etsuhisa Takahashi
Hiroshi Kido
Suehiro Sakaguchi
Neurotropic influenza A virus infection causes prion protein misfolding into infectious prions in neuroblastoma cells
description Abstract Misfolding of the cellular prion protein, PrPC, into the amyloidogenic isoform, PrPSc, 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 PrPC into PrPSc and propagate infectious prions in infected cells. Here, we found that infection with a neurotropic influenza A virus strain (IAV/WSN) caused misfolding of PrPC into PrPSc and generated infectious prions in mouse neuroblastoma cells through a hit-and-run mechanism. The structural and biochemical characteristics of IAV/WSN-induced PrPSc were different from those of RML and 22L laboratory prions-evoked PrPSc, and the pathogenicity of IAV/WSN-induced prions were also different from that of RML and 22L prions, suggesting IAV/WSN-specific formation of PrPSc and infectious prions. Our current results may open a new avenue for the role of viral infection in misfolding of PrPC into PrPSc and formation of infectious prions.
format article
author Hideyuki Hara
Junji Chida
Keiji Uchiyama
Agriani Dini Pasiana
Etsuhisa Takahashi
Hiroshi Kido
Suehiro Sakaguchi
author_facet Hideyuki Hara
Junji Chida
Keiji Uchiyama
Agriani Dini Pasiana
Etsuhisa Takahashi
Hiroshi Kido
Suehiro Sakaguchi
author_sort Hideyuki Hara
title Neurotropic influenza A virus infection causes prion protein misfolding into infectious prions in neuroblastoma cells
title_short Neurotropic influenza A virus infection causes prion protein misfolding into infectious prions in neuroblastoma cells
title_full Neurotropic influenza A virus infection causes prion protein misfolding into infectious prions in neuroblastoma cells
title_fullStr Neurotropic influenza A virus infection causes prion protein misfolding into infectious prions in neuroblastoma cells
title_full_unstemmed Neurotropic influenza A virus infection causes prion protein misfolding into infectious prions in neuroblastoma cells
title_sort neurotropic influenza a virus infection causes prion protein misfolding into infectious prions in neuroblastoma cells
publisher Nature Portfolio
publishDate 2021
url https://doaj.org/article/54c57a68787c4beb8f8d7706db3b0d5c
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