SARS-CoV-2 ORF3a drives dynamic dense body formation for optimal viral infectivity
Abstract SARS-CoV-2 hijacks multiple organelles for virion assembly, of which the mechanisms have not been fully understood. Here, we identified a SARS-CoV-2-driven membrane structure named the 3a dense body (3DB). 3DBs are unusual electron-dense and dynamic structures driven by the accessory protei...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-05-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-59475-x |
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| author | Stella Hartmann Lisa Radochonski Chengjin Ye Luis Martinez-Sobrido Jueqi Chen |
| author_facet | Stella Hartmann Lisa Radochonski Chengjin Ye Luis Martinez-Sobrido Jueqi Chen |
| author_sort | Stella Hartmann |
| collection | DOAJ |
| description | Abstract SARS-CoV-2 hijacks multiple organelles for virion assembly, of which the mechanisms have not been fully understood. Here, we identified a SARS-CoV-2-driven membrane structure named the 3a dense body (3DB). 3DBs are unusual electron-dense and dynamic structures driven by the accessory protein ORF3a via remodeling a specific subset of the trans-Golgi network (TGN) and early endosomal membrane. 3DB formation is conserved in related bat and pangolin coronaviruses but was lost during the evolution to SARS-CoV. During SARS-CoV-2 infection, 3DB recruits the viral structural proteins spike (S) and membrane (M) and undergoes dynamic fusion/fission to maintain the optimal unprocessed-to-processed ratio of S on assembled virions. Disruption of 3DB formation resulted in virions assembled with an abnormal S processing rate, leading to a dramatic reduction in viral entry efficiency. Our study uncovers the crucial role of 3DB in maintaining maximal SARS-CoV-2 infectivity and highlights its potential as a target for COVID-19 prophylactics and therapeutics. |
| format | Article |
| id | doaj-art-da9d2319dd7f4d208faf9b6e7bf1bb79 |
| institution | OA Journals |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-da9d2319dd7f4d208faf9b6e7bf1bb792025-08-20T01:51:28ZengNature PortfolioNature Communications2041-17232025-05-0116112210.1038/s41467-025-59475-xSARS-CoV-2 ORF3a drives dynamic dense body formation for optimal viral infectivityStella Hartmann0Lisa Radochonski1Chengjin Ye2Luis Martinez-Sobrido3Jueqi Chen4Department of Microbiology, University of ChicagoDepartment of Microbiology, University of ChicagoTexas Biomedical Research InstituteTexas Biomedical Research InstituteDepartment of Microbiology, University of ChicagoAbstract SARS-CoV-2 hijacks multiple organelles for virion assembly, of which the mechanisms have not been fully understood. Here, we identified a SARS-CoV-2-driven membrane structure named the 3a dense body (3DB). 3DBs are unusual electron-dense and dynamic structures driven by the accessory protein ORF3a via remodeling a specific subset of the trans-Golgi network (TGN) and early endosomal membrane. 3DB formation is conserved in related bat and pangolin coronaviruses but was lost during the evolution to SARS-CoV. During SARS-CoV-2 infection, 3DB recruits the viral structural proteins spike (S) and membrane (M) and undergoes dynamic fusion/fission to maintain the optimal unprocessed-to-processed ratio of S on assembled virions. Disruption of 3DB formation resulted in virions assembled with an abnormal S processing rate, leading to a dramatic reduction in viral entry efficiency. Our study uncovers the crucial role of 3DB in maintaining maximal SARS-CoV-2 infectivity and highlights its potential as a target for COVID-19 prophylactics and therapeutics.https://doi.org/10.1038/s41467-025-59475-x |
| spellingShingle | Stella Hartmann Lisa Radochonski Chengjin Ye Luis Martinez-Sobrido Jueqi Chen SARS-CoV-2 ORF3a drives dynamic dense body formation for optimal viral infectivity Nature Communications |
| title | SARS-CoV-2 ORF3a drives dynamic dense body formation for optimal viral infectivity |
| title_full | SARS-CoV-2 ORF3a drives dynamic dense body formation for optimal viral infectivity |
| title_fullStr | SARS-CoV-2 ORF3a drives dynamic dense body formation for optimal viral infectivity |
| title_full_unstemmed | SARS-CoV-2 ORF3a drives dynamic dense body formation for optimal viral infectivity |
| title_short | SARS-CoV-2 ORF3a drives dynamic dense body formation for optimal viral infectivity |
| title_sort | sars cov 2 orf3a drives dynamic dense body formation for optimal viral infectivity |
| url | https://doi.org/10.1038/s41467-025-59475-x |
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