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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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2022-12-01
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| Series: | Emerging Microbes and Infections |
| Subjects: | |
| Online Access: | https://www.tandfonline.com/doi/10.1080/22221751.2022.2059403 |
| _version_ | 1811304061767516160 |
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| author | Yun-Qi Zhou Ke Wang Xue-Yan Wang Hong-Yong Cui Yongxiang Zhao Ping Zhu Zhi-Nan Chen |
| author_facet | Yun-Qi Zhou Ke Wang Xue-Yan Wang Hong-Yong Cui Yongxiang Zhao Ping Zhu Zhi-Nan Chen |
| author_sort | Yun-Qi Zhou |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-04-13T08:00:10Z |
| format | Article |
| id | doaj.art-87dade94fdb145869c4fedb680946111 |
| institution | Directory Open Access Journal |
| issn | 2222-1751 |
| language | English |
| last_indexed | 2024-04-13T08:00:10Z |
| publishDate | 2022-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Emerging Microbes and Infections |
| spelling | doaj.art-87dade94fdb145869c4fedb6809461112022-12-22T02:55:18ZengTaylor & Francis GroupEmerging Microbes and Infections2222-17512022-12-011111135114410.1080/22221751.2022.2059403SARS-CoV-2 pseudovirus enters the host cells through spike protein-CD147 in an Arf6-dependent mannerYun-Qi Zhou0Ke Wang1Xue-Yan Wang2Hong-Yong Cui3Yongxiang Zhao4Ping Zhu5Zhi-Nan Chen6National Center for International Research of Bio-targeting Theranostics, Guangxi Key Laboratory of Bio-targeting Theranostics, Collaborative Innovation Center for Targeting Tumor Diagnosis and Therapy, Guangxi Talent Highland of Bio-targeting Theranostics, Guangxi Medical University, Nanning, People’s Republic of ChinaNational Translational Science Center for Molecular Medicine & Department of Cell Biology, Fourth Military Medical University, Xi’an, People’s Republic of ChinaNational Center for International Research of Bio-targeting Theranostics, Guangxi Key Laboratory of Bio-targeting Theranostics, Collaborative Innovation Center for Targeting Tumor Diagnosis and Therapy, Guangxi Talent Highland of Bio-targeting Theranostics, Guangxi Medical University, Nanning, People’s Republic of ChinaNational Translational Science Center for Molecular Medicine & Department of Cell Biology, Fourth Military Medical University, Xi’an, People’s Republic of ChinaNational Center for International Research of Bio-targeting Theranostics, Guangxi Key Laboratory of Bio-targeting Theranostics, Collaborative Innovation Center for Targeting Tumor Diagnosis and Therapy, Guangxi Talent Highland of Bio-targeting Theranostics, Guangxi Medical University, Nanning, People’s Republic of ChinaDepartment of Clinical Immunology, Xijing Hospital, Fourth Military Medical University, Xi’an, People’s Republic of ChinaNational Center for International Research of Bio-targeting Theranostics, Guangxi Key Laboratory of Bio-targeting Theranostics, Collaborative Innovation Center for Targeting Tumor Diagnosis and Therapy, Guangxi Talent Highland of Bio-targeting Theranostics, Guangxi Medical University, Nanning, People’s Republic of ChinaThe 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.https://www.tandfonline.com/doi/10.1080/22221751.2022.2059403SARS-CoV-2CD147endocytosisArf6spike protein |
| spellingShingle | Yun-Qi Zhou Ke Wang Xue-Yan Wang Hong-Yong Cui Yongxiang Zhao Ping Zhu Zhi-Nan Chen SARS-CoV-2 pseudovirus enters the host cells through spike protein-CD147 in an Arf6-dependent manner Emerging Microbes and Infections SARS-CoV-2 CD147 endocytosis Arf6 spike protein |
| 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 | SARS-CoV-2 CD147 endocytosis Arf6 spike protein |
| url | https://www.tandfonline.com/doi/10.1080/22221751.2022.2059403 |
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