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SARS-CoV-2 pseudovirus enters the host cells through spike protein-CD147 in an Arf6-dependent manner

The spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its variants is threatening public health around the world. Endocytosis functions as an important way for viral infection, and SARS-CoV-2 bears no exception. However, the specific endocytic mechanism of SARS-CoV-2 remains...

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Autores principales: Zhou, Yun-Qi, Wang, Ke, Wang, Xue-Yan, Cui, Hong-Yong, Zhao, Yongxiang, Zhu, Ping, Chen, Zhi-Nan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9037224/
https://www.ncbi.nlm.nih.gov/pubmed/35343395
http://dx.doi.org/10.1080/22221751.2022.2059403
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author Zhou, Yun-Qi
Wang, Ke
Wang, Xue-Yan
Cui, Hong-Yong
Zhao, Yongxiang
Zhu, Ping
Chen, Zhi-Nan
author_facet Zhou, Yun-Qi
Wang, Ke
Wang, Xue-Yan
Cui, Hong-Yong
Zhao, Yongxiang
Zhu, Ping
Chen, Zhi-Nan
author_sort Zhou, Yun-Qi
collection PubMed
description The spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its variants is threatening public health around the world. Endocytosis functions as an important way for viral infection, and SARS-CoV-2 bears no exception. However, the specific endocytic mechanism of SARS-CoV-2 remains unknown. In this study, we used endocytic inhibitors to evaluate the role of different endocytic routes in SARS-CoV-2 pseudovirus infection and found that the viral infection was associated with caveolar/lipid raft- and cytoskeleton-mediated endocytosis, but independent of the clathrin-mediated endocytosis and macropinocytosis. Meanwhile, the knockdown of CD147 and Rab5a in Vero E6 and Huh-7 cells inhibited SARS-CoV-2 pseudovirus infection, and the co-localization of spike protein, CD147, and Rab5a was observed in pseudovirus-infected Vero E6 cells, which was weakened by CD147 silencing, illustrating that SARS-CoV-2 pseudovirus entered the host cells via CD147-mediated endocytosis. Additionally, Arf6 silencing markedly inhibited pseudovirus infection in Vero E6 and Huh-7 cells, while little change was observed in CD147 knockout-Vero E6 cells. This finding indicated Arf6-mediated CD147 trafficking plays a vital role in SARS-CoV-2 entry. Taken together, our findings provide new insights into the CD147-Arf6 axis in mediating SARS-CoV-2 pseudovirus entry into the host cells, and further suggest that blockade of this pathway seems to be a feasible approach to prevent the SARS-CoV-2 infection clinically.
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spelling pubmed-90372242022-04-26 SARS-CoV-2 pseudovirus enters the host cells through spike protein-CD147 in an Arf6-dependent manner Zhou, Yun-Qi Wang, Ke Wang, Xue-Yan Cui, Hong-Yong Zhao, Yongxiang Zhu, Ping Chen, Zhi-Nan Emerg Microbes Infect Research Article The spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its variants is threatening public health around the world. Endocytosis functions as an important way for viral infection, and SARS-CoV-2 bears no exception. However, the specific endocytic mechanism of SARS-CoV-2 remains unknown. In this study, we used endocytic inhibitors to evaluate the role of different endocytic routes in SARS-CoV-2 pseudovirus infection and found that the viral infection was associated with caveolar/lipid raft- and cytoskeleton-mediated endocytosis, but independent of the clathrin-mediated endocytosis and macropinocytosis. Meanwhile, the knockdown of CD147 and Rab5a in Vero E6 and Huh-7 cells inhibited SARS-CoV-2 pseudovirus infection, and the co-localization of spike protein, CD147, and Rab5a was observed in pseudovirus-infected Vero E6 cells, which was weakened by CD147 silencing, illustrating that SARS-CoV-2 pseudovirus entered the host cells via CD147-mediated endocytosis. Additionally, Arf6 silencing markedly inhibited pseudovirus infection in Vero E6 and Huh-7 cells, while little change was observed in CD147 knockout-Vero E6 cells. This finding indicated Arf6-mediated CD147 trafficking plays a vital role in SARS-CoV-2 entry. Taken together, our findings provide new insights into the CD147-Arf6 axis in mediating SARS-CoV-2 pseudovirus entry into the host cells, and further suggest that blockade of this pathway seems to be a feasible approach to prevent the SARS-CoV-2 infection clinically. Taylor & Francis 2022-04-18 /pmc/articles/PMC9037224/ /pubmed/35343395 http://dx.doi.org/10.1080/22221751.2022.2059403 Text en © 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) ), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Zhou, Yun-Qi
Wang, Ke
Wang, Xue-Yan
Cui, Hong-Yong
Zhao, Yongxiang
Zhu, Ping
Chen, Zhi-Nan
SARS-CoV-2 pseudovirus enters the host cells through spike protein-CD147 in an Arf6-dependent manner
title SARS-CoV-2 pseudovirus enters the host cells through spike protein-CD147 in an Arf6-dependent manner
title_full SARS-CoV-2 pseudovirus enters the host cells through spike protein-CD147 in an Arf6-dependent manner
title_fullStr SARS-CoV-2 pseudovirus enters the host cells through spike protein-CD147 in an Arf6-dependent manner
title_full_unstemmed SARS-CoV-2 pseudovirus enters the host cells through spike protein-CD147 in an Arf6-dependent manner
title_short SARS-CoV-2 pseudovirus enters the host cells through spike protein-CD147 in an Arf6-dependent manner
title_sort sars-cov-2 pseudovirus enters the host cells through spike protein-cd147 in an arf6-dependent manner
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9037224/
https://www.ncbi.nlm.nih.gov/pubmed/35343395
http://dx.doi.org/10.1080/22221751.2022.2059403
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