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SARS-CoV-2 impairs the disassembly of stress granules and promotes ALS-associated amyloid aggregation
The nucleocapsid (N) protein of SARS-CoV-2 has been reported to have a high ability of liquid-liquid phase separation, which enables its incorporation into stress granules (SGs) of host cells. However, whether SG invasion by N protein occurs in the scenario of SARS-CoV-2 infection is unknow, neither...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Higher Education Press
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8983322/ https://www.ncbi.nlm.nih.gov/pubmed/35384603 http://dx.doi.org/10.1007/s13238-022-00905-7 |
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author | Li, Yichen Lu, Shuaiyao Gu, Jinge Xia, Wencheng Zhang, Shengnan Zhang, Shenqing Wang, Yan Zhang, Chong Sun, Yunpeng Lei, Jian Liu, Cong Su, Zhaoming Yang, Juntao Peng, Xiaozhong Li, Dan |
author_facet | Li, Yichen Lu, Shuaiyao Gu, Jinge Xia, Wencheng Zhang, Shengnan Zhang, Shenqing Wang, Yan Zhang, Chong Sun, Yunpeng Lei, Jian Liu, Cong Su, Zhaoming Yang, Juntao Peng, Xiaozhong Li, Dan |
author_sort | Li, Yichen |
collection | PubMed |
description | The nucleocapsid (N) protein of SARS-CoV-2 has been reported to have a high ability of liquid-liquid phase separation, which enables its incorporation into stress granules (SGs) of host cells. However, whether SG invasion by N protein occurs in the scenario of SARS-CoV-2 infection is unknow, neither do we know its consequence. Here, we used SARS-CoV-2 to infect mammalian cells and observed the incorporation of N protein into SGs, which resulted in markedly impaired self-disassembly but stimulated cell cellular clearance of SGs. NMR experiments further showed that N protein binds to the SG-related amyloid proteins via non-specific transient interactions, which not only expedites the phase transition of these proteins to aberrant amyloid aggregation in vitro, but also promotes the aggregation of FUS with ALS-associated P525L mutation in cells. In addition, we found that ACE2 is not necessary for the infection of SARS-CoV-2 to mammalian cells. Our work indicates that SARS-CoV-2 infection can impair the disassembly of host SGs and promote the aggregation of SG-related amyloid proteins, which may lead to an increased risk of neurodegeneration. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13238-022-00905-7. |
format | Online Article Text |
id | pubmed-8983322 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Higher Education Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-89833222022-04-06 SARS-CoV-2 impairs the disassembly of stress granules and promotes ALS-associated amyloid aggregation Li, Yichen Lu, Shuaiyao Gu, Jinge Xia, Wencheng Zhang, Shengnan Zhang, Shenqing Wang, Yan Zhang, Chong Sun, Yunpeng Lei, Jian Liu, Cong Su, Zhaoming Yang, Juntao Peng, Xiaozhong Li, Dan Protein Cell Research Article The nucleocapsid (N) protein of SARS-CoV-2 has been reported to have a high ability of liquid-liquid phase separation, which enables its incorporation into stress granules (SGs) of host cells. However, whether SG invasion by N protein occurs in the scenario of SARS-CoV-2 infection is unknow, neither do we know its consequence. Here, we used SARS-CoV-2 to infect mammalian cells and observed the incorporation of N protein into SGs, which resulted in markedly impaired self-disassembly but stimulated cell cellular clearance of SGs. NMR experiments further showed that N protein binds to the SG-related amyloid proteins via non-specific transient interactions, which not only expedites the phase transition of these proteins to aberrant amyloid aggregation in vitro, but also promotes the aggregation of FUS with ALS-associated P525L mutation in cells. In addition, we found that ACE2 is not necessary for the infection of SARS-CoV-2 to mammalian cells. Our work indicates that SARS-CoV-2 infection can impair the disassembly of host SGs and promote the aggregation of SG-related amyloid proteins, which may lead to an increased risk of neurodegeneration. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13238-022-00905-7. Higher Education Press 2022-04-06 2022-08 /pmc/articles/PMC8983322/ /pubmed/35384603 http://dx.doi.org/10.1007/s13238-022-00905-7 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Research Article Li, Yichen Lu, Shuaiyao Gu, Jinge Xia, Wencheng Zhang, Shengnan Zhang, Shenqing Wang, Yan Zhang, Chong Sun, Yunpeng Lei, Jian Liu, Cong Su, Zhaoming Yang, Juntao Peng, Xiaozhong Li, Dan SARS-CoV-2 impairs the disassembly of stress granules and promotes ALS-associated amyloid aggregation |
title | SARS-CoV-2 impairs the disassembly of stress granules and promotes ALS-associated amyloid aggregation |
title_full | SARS-CoV-2 impairs the disassembly of stress granules and promotes ALS-associated amyloid aggregation |
title_fullStr | SARS-CoV-2 impairs the disassembly of stress granules and promotes ALS-associated amyloid aggregation |
title_full_unstemmed | SARS-CoV-2 impairs the disassembly of stress granules and promotes ALS-associated amyloid aggregation |
title_short | SARS-CoV-2 impairs the disassembly of stress granules and promotes ALS-associated amyloid aggregation |
title_sort | sars-cov-2 impairs the disassembly of stress granules and promotes als-associated amyloid aggregation |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8983322/ https://www.ncbi.nlm.nih.gov/pubmed/35384603 http://dx.doi.org/10.1007/s13238-022-00905-7 |
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