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Cathepsin B Protease Facilitates Chikungunya Virus Envelope Protein-Mediated Infection Via Endocytosis or Macropinocytosis

Chikungunya virus (CHIKV) is an enveloped virus that enters host cells and transits within the endosomes before starting its replication cycle, the precise mechanism of which is yet to be elucidated. Endocytosis and endosome acidification inhibitors inhibit infection by CHIKV, murine leukemia virus...

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Autores principales: Izumida, Mai, Hayashi, Hideki, Tanaka, Atsushi, Kubo, Yoshinao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7412492/
https://www.ncbi.nlm.nih.gov/pubmed/32635194
http://dx.doi.org/10.3390/v12070722
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author Izumida, Mai
Hayashi, Hideki
Tanaka, Atsushi
Kubo, Yoshinao
author_facet Izumida, Mai
Hayashi, Hideki
Tanaka, Atsushi
Kubo, Yoshinao
author_sort Izumida, Mai
collection PubMed
description Chikungunya virus (CHIKV) is an enveloped virus that enters host cells and transits within the endosomes before starting its replication cycle, the precise mechanism of which is yet to be elucidated. Endocytosis and endosome acidification inhibitors inhibit infection by CHIKV, murine leukemia virus (MLV), or SARS-coronavirus, indicating that these viral entries into host cells occur through endosomes and require endosome acidification. Although endosomal cathepsin B protease is necessary for MLV, Ebola virus, and SARS-CoV infections, its role in CHIKV infection is unknown. Our results revealed that endocytosis inhibitors attenuated CHIKV-pseudotyped MLV vector infection in 293T cells but not in TE671 cells. In contrast, macropinocytosis inhibitors attenuated CHIKV-pseudotyped MLV vector infection in TE671 cells but not in 293T cells, suggesting that CHIKV host cell entry occurs via endocytosis or macropinocytosis, depending on the cell lines used. Cathepsin B inhibitor and knockdown by an shRNA suppressed CHIKV-pseudotyped MLV vector infection both in 293T and TE671 cells. These results show that cathepsin B facilitates CHIKV infection regardless of the entry pathway.
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spelling pubmed-74124922020-08-26 Cathepsin B Protease Facilitates Chikungunya Virus Envelope Protein-Mediated Infection Via Endocytosis or Macropinocytosis Izumida, Mai Hayashi, Hideki Tanaka, Atsushi Kubo, Yoshinao Viruses Article Chikungunya virus (CHIKV) is an enveloped virus that enters host cells and transits within the endosomes before starting its replication cycle, the precise mechanism of which is yet to be elucidated. Endocytosis and endosome acidification inhibitors inhibit infection by CHIKV, murine leukemia virus (MLV), or SARS-coronavirus, indicating that these viral entries into host cells occur through endosomes and require endosome acidification. Although endosomal cathepsin B protease is necessary for MLV, Ebola virus, and SARS-CoV infections, its role in CHIKV infection is unknown. Our results revealed that endocytosis inhibitors attenuated CHIKV-pseudotyped MLV vector infection in 293T cells but not in TE671 cells. In contrast, macropinocytosis inhibitors attenuated CHIKV-pseudotyped MLV vector infection in TE671 cells but not in 293T cells, suggesting that CHIKV host cell entry occurs via endocytosis or macropinocytosis, depending on the cell lines used. Cathepsin B inhibitor and knockdown by an shRNA suppressed CHIKV-pseudotyped MLV vector infection both in 293T and TE671 cells. These results show that cathepsin B facilitates CHIKV infection regardless of the entry pathway. MDPI 2020-07-03 /pmc/articles/PMC7412492/ /pubmed/32635194 http://dx.doi.org/10.3390/v12070722 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Izumida, Mai
Hayashi, Hideki
Tanaka, Atsushi
Kubo, Yoshinao
Cathepsin B Protease Facilitates Chikungunya Virus Envelope Protein-Mediated Infection Via Endocytosis or Macropinocytosis
title Cathepsin B Protease Facilitates Chikungunya Virus Envelope Protein-Mediated Infection Via Endocytosis or Macropinocytosis
title_full Cathepsin B Protease Facilitates Chikungunya Virus Envelope Protein-Mediated Infection Via Endocytosis or Macropinocytosis
title_fullStr Cathepsin B Protease Facilitates Chikungunya Virus Envelope Protein-Mediated Infection Via Endocytosis or Macropinocytosis
title_full_unstemmed Cathepsin B Protease Facilitates Chikungunya Virus Envelope Protein-Mediated Infection Via Endocytosis or Macropinocytosis
title_short Cathepsin B Protease Facilitates Chikungunya Virus Envelope Protein-Mediated Infection Via Endocytosis or Macropinocytosis
title_sort cathepsin b protease facilitates chikungunya virus envelope protein-mediated infection via endocytosis or macropinocytosis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7412492/
https://www.ncbi.nlm.nih.gov/pubmed/32635194
http://dx.doi.org/10.3390/v12070722
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