SARS-CoV-2 ORF3a Induces Incomplete Autophagy via the Unfolded Protein Response
In the past year and a half, SARS-CoV-2 has caused 240 million confirmed cases and 5 million deaths worldwide. Autophagy is a conserved process that either promotes or inhibits viral infections. Although coronaviruses are known to utilize the transport of autophagy-dependent vesicles for the viral l...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-12-01
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| Series: | Viruses |
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| Online Access: | https://www.mdpi.com/1999-4915/13/12/2467 |
| _version_ | 1827668976034906112 |
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| author | Wen-qing Su Xue-jie Yu Chuan-min Zhou |
| author_facet | Wen-qing Su Xue-jie Yu Chuan-min Zhou |
| author_sort | Wen-qing Su |
| collection | DOAJ |
| description | In the past year and a half, SARS-CoV-2 has caused 240 million confirmed cases and 5 million deaths worldwide. Autophagy is a conserved process that either promotes or inhibits viral infections. Although coronaviruses are known to utilize the transport of autophagy-dependent vesicles for the viral life cycle, the underlying autophagy-inducing mechanisms remain largely unexplored. Using several autophagy-deficient cell lines and autophagy inhibitors, we demonstrated that SARS-CoV-2 ORF3a was able to induce incomplete autophagy in a FIP200/Beclin-1-dependent manner. Moreover, ORF3a was involved in the induction of the UPR (unfolded protein response), while the IRE1 and ATF6 pathways, but not the PERK pathway, were responsible for mediating the ORF3a-induced autophagy. These results identify the role of the UPR pathway in the ORF3a-induced classical autophagy process, which may provide us with a better understanding of SARS-CoV-2 and suggest new therapeutic modalities in the treatment of COVID-19. |
| first_indexed | 2024-03-10T03:54:04Z |
| format | Article |
| id | doaj.art-53eaaf677bd442caac38a7189261835a |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-03-10T03:54:04Z |
| publishDate | 2021-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-53eaaf677bd442caac38a7189261835a2023-11-23T10:58:20ZengMDPI AGViruses1999-49152021-12-011312246710.3390/v13122467SARS-CoV-2 ORF3a Induces Incomplete Autophagy via the Unfolded Protein ResponseWen-qing Su0Xue-jie Yu1Chuan-min Zhou2State Key Laboratory of Virology, School of Public Health, Wuhan University, Wuhan 430071, ChinaState Key Laboratory of Virology, School of Public Health, Wuhan University, Wuhan 430071, ChinaState Key Laboratory of Virology, School of Public Health, Wuhan University, Wuhan 430071, ChinaIn the past year and a half, SARS-CoV-2 has caused 240 million confirmed cases and 5 million deaths worldwide. Autophagy is a conserved process that either promotes or inhibits viral infections. Although coronaviruses are known to utilize the transport of autophagy-dependent vesicles for the viral life cycle, the underlying autophagy-inducing mechanisms remain largely unexplored. Using several autophagy-deficient cell lines and autophagy inhibitors, we demonstrated that SARS-CoV-2 ORF3a was able to induce incomplete autophagy in a FIP200/Beclin-1-dependent manner. Moreover, ORF3a was involved in the induction of the UPR (unfolded protein response), while the IRE1 and ATF6 pathways, but not the PERK pathway, were responsible for mediating the ORF3a-induced autophagy. These results identify the role of the UPR pathway in the ORF3a-induced classical autophagy process, which may provide us with a better understanding of SARS-CoV-2 and suggest new therapeutic modalities in the treatment of COVID-19.https://www.mdpi.com/1999-4915/13/12/2467coronavirusSARS-CoV-2autophagyORF3aUPR |
| spellingShingle | Wen-qing Su Xue-jie Yu Chuan-min Zhou SARS-CoV-2 ORF3a Induces Incomplete Autophagy via the Unfolded Protein Response Viruses coronavirus SARS-CoV-2 autophagy ORF3a UPR |
| title | SARS-CoV-2 ORF3a Induces Incomplete Autophagy via the Unfolded Protein Response |
| title_full | SARS-CoV-2 ORF3a Induces Incomplete Autophagy via the Unfolded Protein Response |
| title_fullStr | SARS-CoV-2 ORF3a Induces Incomplete Autophagy via the Unfolded Protein Response |
| title_full_unstemmed | SARS-CoV-2 ORF3a Induces Incomplete Autophagy via the Unfolded Protein Response |
| title_short | SARS-CoV-2 ORF3a Induces Incomplete Autophagy via the Unfolded Protein Response |
| title_sort | sars cov 2 orf3a induces incomplete autophagy via the unfolded protein response |
| topic | coronavirus SARS-CoV-2 autophagy ORF3a UPR |
| url | https://www.mdpi.com/1999-4915/13/12/2467 |
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