Prion strains depend on different endocytic routes for productive infection

Abstract Prions are unconventional agents composed of misfolded prion protein that cause fatal neurodegenerative diseases in mammals. Prion strains induce specific neuropathological changes in selected brain areas. The mechanism of strain-specific cell tropism is unknown. We hypothesised that prion...

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Autores principales:	Andrea Fehlinger, Hanna Wolf, André Hossinger, Yvonne Duernberger, Catharina Pleschka, Katrin Riemschoss, Shu Liu, Romina Bester, Lydia Paulsen, Suzette A. Priola, Martin H. Groschup, Hermann M. Schätzl, Ina M. Vorberg
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/13fe002f36ce4b6588374aa799d3ba3e
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spelling	oai:doaj.org-article:13fe002f36ce4b6588374aa799d3ba3e2021-12-02T12:32:43ZPrion strains depend on different endocytic routes for productive infection10.1038/s41598-017-07260-22045-2322https://doaj.org/article/13fe002f36ce4b6588374aa799d3ba3e2017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-07260-2https://doaj.org/toc/2045-2322Abstract Prions are unconventional agents composed of misfolded prion protein that cause fatal neurodegenerative diseases in mammals. Prion strains induce specific neuropathological changes in selected brain areas. The mechanism of strain-specific cell tropism is unknown. We hypothesised that prion strains rely on different endocytic routes to invade and replicate within their target cells. Using prion permissive cells, we determined how impairment of endocytosis affects productive infection by prion strains 22L and RML. We demonstrate that early and late stages of prion infection are differentially sensitive to perturbation of clathrin- and caveolin-mediated endocytosis. Manipulation of canonical endocytic pathways only slightly influenced prion uptake. However, blocking the same routes had drastic strain-specific consequences on the establishment of infection. Our data argue that prion strains use different endocytic pathways for infection and suggest that cell type-dependent differences in prion uptake could contribute to host cell tropism.Andrea FehlingerHanna WolfAndré HossingerYvonne DuernbergerCatharina PleschkaKatrin RiemschossShu LiuRomina BesterLydia PaulsenSuzette A. PriolaMartin H. GroschupHermann M. SchätzlIna M. VorbergNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-15 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Andrea Fehlinger Hanna Wolf André Hossinger Yvonne Duernberger Catharina Pleschka Katrin Riemschoss Shu Liu Romina Bester Lydia Paulsen Suzette A. Priola Martin H. Groschup Hermann M. Schätzl Ina M. Vorberg Prion strains depend on different endocytic routes for productive infection
description	Abstract Prions are unconventional agents composed of misfolded prion protein that cause fatal neurodegenerative diseases in mammals. Prion strains induce specific neuropathological changes in selected brain areas. The mechanism of strain-specific cell tropism is unknown. We hypothesised that prion strains rely on different endocytic routes to invade and replicate within their target cells. Using prion permissive cells, we determined how impairment of endocytosis affects productive infection by prion strains 22L and RML. We demonstrate that early and late stages of prion infection are differentially sensitive to perturbation of clathrin- and caveolin-mediated endocytosis. Manipulation of canonical endocytic pathways only slightly influenced prion uptake. However, blocking the same routes had drastic strain-specific consequences on the establishment of infection. Our data argue that prion strains use different endocytic pathways for infection and suggest that cell type-dependent differences in prion uptake could contribute to host cell tropism.
format	article
author	Andrea Fehlinger Hanna Wolf André Hossinger Yvonne Duernberger Catharina Pleschka Katrin Riemschoss Shu Liu Romina Bester Lydia Paulsen Suzette A. Priola Martin H. Groschup Hermann M. Schätzl Ina M. Vorberg
author_facet	Andrea Fehlinger Hanna Wolf André Hossinger Yvonne Duernberger Catharina Pleschka Katrin Riemschoss Shu Liu Romina Bester Lydia Paulsen Suzette A. Priola Martin H. Groschup Hermann M. Schätzl Ina M. Vorberg
author_sort	Andrea Fehlinger
title	Prion strains depend on different endocytic routes for productive infection
title_short	Prion strains depend on different endocytic routes for productive infection
title_full	Prion strains depend on different endocytic routes for productive infection
title_fullStr	Prion strains depend on different endocytic routes for productive infection
title_full_unstemmed	Prion strains depend on different endocytic routes for productive infection
title_sort	prion strains depend on different endocytic routes for productive infection
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/13fe002f36ce4b6588374aa799d3ba3e
work_keys_str_mv	AT andreafehlinger prionstrainsdependondifferentendocyticroutesforproductiveinfection AT hannawolf prionstrainsdependondifferentendocyticroutesforproductiveinfection AT andrehossinger prionstrainsdependondifferentendocyticroutesforproductiveinfection AT yvonneduernberger prionstrainsdependondifferentendocyticroutesforproductiveinfection AT catharinapleschka prionstrainsdependondifferentendocyticroutesforproductiveinfection AT katrinriemschoss prionstrainsdependondifferentendocyticroutesforproductiveinfection AT shuliu prionstrainsdependondifferentendocyticroutesforproductiveinfection AT rominabester prionstrainsdependondifferentendocyticroutesforproductiveinfection AT lydiapaulsen prionstrainsdependondifferentendocyticroutesforproductiveinfection AT suzetteapriola prionstrainsdependondifferentendocyticroutesforproductiveinfection AT martinhgroschup prionstrainsdependondifferentendocyticroutesforproductiveinfection AT hermannmschatzl prionstrainsdependondifferentendocyticroutesforproductiveinfection AT inamvorberg prionstrainsdependondifferentendocyticroutesforproductiveinfection
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Prion strains depend on different endocytic routes for productive infection

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