Aggregation potency and proinflammatory effects of SARS-CoV-2 proteins
Abstract Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, is primarily known as a respiratory disease. The continued study of the disease has shown that long-term COVID-19 symptoms include persisting effects of the virus on the br...
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Nature Portfolio
2025-08-01
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| Online Access: | https://doi.org/10.1038/s41598-025-10013-1 |
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| author | Monica Costa Da-Wei Wang Kai-Dong Zhao Lin Yuan Anita Krisko Jia-Yi Li Tiago Outeiro Wen Li |
| author_facet | Monica Costa Da-Wei Wang Kai-Dong Zhao Lin Yuan Anita Krisko Jia-Yi Li Tiago Outeiro Wen Li |
| author_sort | Monica Costa |
| collection | DOAJ |
| description | Abstract Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, is primarily known as a respiratory disease. The continued study of the disease has shown that long-term COVID-19 symptoms include persisting effects of the virus on the brain when the infection is over, possibly even leading to neurodegeneration. However, the exact mechanisms of nervous system damage induced by SARS-CoV-2 are still unclear. In this study, we focused on two possibly shared pathways of SARS-CoV-2-induced neural dysfunction and neurodegeneration: protein aggregation, which is associated with impaired protein clearance, and inflammatory responses, which involve a hyper-active immune status. We observed distinct expression and distribution patterns of ten SARS-CoV-2 proteins in the two cell lines, meanwhile forming aggregation puncta and inducing pro-inflammatory responses. We found that the ER stress was induced and that the autophagy-lysosome pathway was inhibited upon viral protein expression. Boosting autophagy function attenuated protein aggregation, suggesting that modulation of autophagy might be a valid strategy for inhibiting cytotoxic effects of SARS-CoV- 2 proteins. Our study provides potential explanations of SARS-CoV-2-induced cell damage, based on shared cellular mechanisms and furthermore, suggests that modulation of proteostasis may serve as therapeutic strategies for preventing long-lasting SARS-CoV-2 cytotoxic effects. |
| format | Article |
| id | doaj-art-df2b8bceec1a4235ba0ff8994190f2f4 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
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| spelling | doaj-art-df2b8bceec1a4235ba0ff8994190f2f42025-08-20T03:45:49ZengNature PortfolioScientific Reports2045-23222025-08-0115111710.1038/s41598-025-10013-1Aggregation potency and proinflammatory effects of SARS-CoV-2 proteinsMonica Costa0Da-Wei Wang1Kai-Dong Zhao2Lin Yuan3Anita Krisko4Jia-Yi Li5Tiago Outeiro6Wen Li7Department of Experimental Neurodegeneration, Center for Biostructural Imaging of Neurodegeneration, University Medical Center GöttingenDepartment of Experimental Neurodegeneration, Center for Biostructural Imaging of Neurodegeneration, University Medical Center GöttingenLaboratory of Research in Parkinson’s and Related Disorders, Key Laboratory of Major Chronic Diseases of Nervous System of Liaoning Province, Health Sciences Institute, China Medical UniversityLaboratory of Research in Parkinson’s and Related Disorders, Key Laboratory of Major Chronic Diseases of Nervous System of Liaoning Province, Health Sciences Institute, China Medical UniversityDepartment of Experimental Neurodegeneration, Center for Biostructural Imaging of Neurodegeneration, University Medical Center GöttingenLaboratory of Research in Parkinson’s and Related Disorders, Key Laboratory of Major Chronic Diseases of Nervous System of Liaoning Province, Health Sciences Institute, China Medical UniversityDepartment of Experimental Neurodegeneration, Center for Biostructural Imaging of Neurodegeneration, University Medical Center GöttingenLaboratory of Research in Parkinson’s and Related Disorders, Key Laboratory of Major Chronic Diseases of Nervous System of Liaoning Province, Health Sciences Institute, China Medical UniversityAbstract Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, is primarily known as a respiratory disease. The continued study of the disease has shown that long-term COVID-19 symptoms include persisting effects of the virus on the brain when the infection is over, possibly even leading to neurodegeneration. However, the exact mechanisms of nervous system damage induced by SARS-CoV-2 are still unclear. In this study, we focused on two possibly shared pathways of SARS-CoV-2-induced neural dysfunction and neurodegeneration: protein aggregation, which is associated with impaired protein clearance, and inflammatory responses, which involve a hyper-active immune status. We observed distinct expression and distribution patterns of ten SARS-CoV-2 proteins in the two cell lines, meanwhile forming aggregation puncta and inducing pro-inflammatory responses. We found that the ER stress was induced and that the autophagy-lysosome pathway was inhibited upon viral protein expression. Boosting autophagy function attenuated protein aggregation, suggesting that modulation of autophagy might be a valid strategy for inhibiting cytotoxic effects of SARS-CoV- 2 proteins. Our study provides potential explanations of SARS-CoV-2-induced cell damage, based on shared cellular mechanisms and furthermore, suggests that modulation of proteostasis may serve as therapeutic strategies for preventing long-lasting SARS-CoV-2 cytotoxic effects.https://doi.org/10.1038/s41598-025-10013-1SARS-CoV-2 proteinNeurodegenerationCoronavirus disease 2019InflammationProtein aggregation |
| spellingShingle | Monica Costa Da-Wei Wang Kai-Dong Zhao Lin Yuan Anita Krisko Jia-Yi Li Tiago Outeiro Wen Li Aggregation potency and proinflammatory effects of SARS-CoV-2 proteins Scientific Reports SARS-CoV-2 protein Neurodegeneration Coronavirus disease 2019 Inflammation Protein aggregation |
| title | Aggregation potency and proinflammatory effects of SARS-CoV-2 proteins |
| title_full | Aggregation potency and proinflammatory effects of SARS-CoV-2 proteins |
| title_fullStr | Aggregation potency and proinflammatory effects of SARS-CoV-2 proteins |
| title_full_unstemmed | Aggregation potency and proinflammatory effects of SARS-CoV-2 proteins |
| title_short | Aggregation potency and proinflammatory effects of SARS-CoV-2 proteins |
| title_sort | aggregation potency and proinflammatory effects of sars cov 2 proteins |
| topic | SARS-CoV-2 protein Neurodegeneration Coronavirus disease 2019 Inflammation Protein aggregation |
| url | https://doi.org/10.1038/s41598-025-10013-1 |
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