Extracellular vesicles mediate antibody-resistant transmission of SARS-CoV-2
Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic. Antibody resistance dampens neutralizing antibody therapy and threatens current global Coronavirus (COVID-19) vaccine campaigns. In addition to the emergence of resistant SARS-CoV-2 variants, little i...
| Main Authors: | , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2023-01-01
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| Series: | Cell Discovery |
| Online Access: | https://doi.org/10.1038/s41421-022-00510-2 |
| _version_ | 1797958833080893440 |
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| author | Bingqing Xia Xiaoyan Pan Rong-Hua Luo Xurui Shen Shuangqu Li Yi Wang Xiaoli Zuo Yan Wu Yingqi Guo Gengfu Xiao Qiguang Li Xin-Yan Long Xiao-Yan He Hong-Yi Zheng Ying Lu Wei Pang Yong-Tang Zheng Jia Li Lei-Ke Zhang Zhaobing Gao |
| author_facet | Bingqing Xia Xiaoyan Pan Rong-Hua Luo Xurui Shen Shuangqu Li Yi Wang Xiaoli Zuo Yan Wu Yingqi Guo Gengfu Xiao Qiguang Li Xin-Yan Long Xiao-Yan He Hong-Yi Zheng Ying Lu Wei Pang Yong-Tang Zheng Jia Li Lei-Ke Zhang Zhaobing Gao |
| author_sort | Bingqing Xia |
| collection | DOAJ |
| description | Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic. Antibody resistance dampens neutralizing antibody therapy and threatens current global Coronavirus (COVID-19) vaccine campaigns. In addition to the emergence of resistant SARS-CoV-2 variants, little is known about how SARS-CoV-2 evades antibodies. Here, we report a novel mechanism of extracellular vesicle (EV)-mediated cell-to-cell transmission of SARS-CoV-2, which facilitates SARS-CoV-2 to escape from neutralizing antibodies. These EVs, initially observed in SARS-CoV-2 envelope protein-expressing cells, are secreted by various SARS-CoV-2-infected cells, including Vero E6, Calu-3, and HPAEpiC cells, undergoing infection-induced pyroptosis. Various SARS-CoV-2-infected cells produce similar EVs characterized by extra-large sizes (1.6–9.5 μm in diameter, average diameter > 4.2 μm) much larger than previously reported virus-generated vesicles. Transmission electron microscopy analysis and plaque assay reveal that these SARS-CoV-2-induced EVs contain large amounts of live virus particles. In particular, the vesicle-cloaked SARS-CoV-2 virus is resistant to neutralizing antibodies and able to reinfect naïve cells independent of the reported receptors and cofactors. Consistently, the constructed 3D images show that intact EVs could be taken up by recipient cells directly, supporting vesicle-mediated cell-to-cell transmission of SARS-CoV-2. Our findings reveal a novel mechanism of receptor-independent SARS-CoV-2 infection via cell-to-cell transmission, provide new insights into antibody resistance of SARS-CoV-2 and suggest potential targets for future antiviral therapeutics. |
| first_indexed | 2024-04-11T00:25:29Z |
| format | Article |
| id | doaj.art-c305719166254cf8b55042c190663290 |
| institution | Directory Open Access Journal |
| issn | 2056-5968 |
| language | English |
| last_indexed | 2024-04-11T00:25:29Z |
| publishDate | 2023-01-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Discovery |
| spelling | doaj.art-c305719166254cf8b55042c1906632902023-01-08T12:04:35ZengNature Publishing GroupCell Discovery2056-59682023-01-019111510.1038/s41421-022-00510-2Extracellular vesicles mediate antibody-resistant transmission of SARS-CoV-2Bingqing Xia0Xiaoyan Pan1Rong-Hua Luo2Xurui Shen3Shuangqu Li4Yi Wang5Xiaoli Zuo6Yan Wu7Yingqi Guo8Gengfu Xiao9Qiguang Li10Xin-Yan Long11Xiao-Yan He12Hong-Yi Zheng13Ying Lu14Wei Pang15Yong-Tang Zheng16Jia Li17Lei-Ke Zhang18Zhaobing Gao19Stake Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of SciencesState Key Laboratory of Virology, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of SciencesKey Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Chinese Academy of SciencesStake Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of SciencesStake Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of SciencesStake Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of SciencesStake Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of SciencesState Key Laboratory of Virology, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of SciencesPublic Technology Service Center, Kunming Institute of Zoology, Chinese Academy of SciencesState Key Laboratory of Virology, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of SciencesStake Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of SciencesKey Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Chinese Academy of SciencesKey Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Chinese Academy of SciencesKey Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Chinese Academy of SciencesKey Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Chinese Academy of SciencesKey Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Chinese Academy of SciencesKey Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Chinese Academy of SciencesStake Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of SciencesState Key Laboratory of Virology, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of SciencesStake Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of SciencesAbstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic. Antibody resistance dampens neutralizing antibody therapy and threatens current global Coronavirus (COVID-19) vaccine campaigns. In addition to the emergence of resistant SARS-CoV-2 variants, little is known about how SARS-CoV-2 evades antibodies. Here, we report a novel mechanism of extracellular vesicle (EV)-mediated cell-to-cell transmission of SARS-CoV-2, which facilitates SARS-CoV-2 to escape from neutralizing antibodies. These EVs, initially observed in SARS-CoV-2 envelope protein-expressing cells, are secreted by various SARS-CoV-2-infected cells, including Vero E6, Calu-3, and HPAEpiC cells, undergoing infection-induced pyroptosis. Various SARS-CoV-2-infected cells produce similar EVs characterized by extra-large sizes (1.6–9.5 μm in diameter, average diameter > 4.2 μm) much larger than previously reported virus-generated vesicles. Transmission electron microscopy analysis and plaque assay reveal that these SARS-CoV-2-induced EVs contain large amounts of live virus particles. In particular, the vesicle-cloaked SARS-CoV-2 virus is resistant to neutralizing antibodies and able to reinfect naïve cells independent of the reported receptors and cofactors. Consistently, the constructed 3D images show that intact EVs could be taken up by recipient cells directly, supporting vesicle-mediated cell-to-cell transmission of SARS-CoV-2. Our findings reveal a novel mechanism of receptor-independent SARS-CoV-2 infection via cell-to-cell transmission, provide new insights into antibody resistance of SARS-CoV-2 and suggest potential targets for future antiviral therapeutics.https://doi.org/10.1038/s41421-022-00510-2 |
| spellingShingle | Bingqing Xia Xiaoyan Pan Rong-Hua Luo Xurui Shen Shuangqu Li Yi Wang Xiaoli Zuo Yan Wu Yingqi Guo Gengfu Xiao Qiguang Li Xin-Yan Long Xiao-Yan He Hong-Yi Zheng Ying Lu Wei Pang Yong-Tang Zheng Jia Li Lei-Ke Zhang Zhaobing Gao Extracellular vesicles mediate antibody-resistant transmission of SARS-CoV-2 Cell Discovery |
| title | Extracellular vesicles mediate antibody-resistant transmission of SARS-CoV-2 |
| title_full | Extracellular vesicles mediate antibody-resistant transmission of SARS-CoV-2 |
| title_fullStr | Extracellular vesicles mediate antibody-resistant transmission of SARS-CoV-2 |
| title_full_unstemmed | Extracellular vesicles mediate antibody-resistant transmission of SARS-CoV-2 |
| title_short | Extracellular vesicles mediate antibody-resistant transmission of SARS-CoV-2 |
| title_sort | extracellular vesicles mediate antibody resistant transmission of sars cov 2 |
| url | https://doi.org/10.1038/s41421-022-00510-2 |
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