Omicron subvariant BA.5 efficiently infects lung cells
Abstract The SARS-CoV-2 Omicron subvariants BA.1 and BA.2 exhibit reduced lung cell infection relative to previously circulating SARS-CoV-2 variants, which may account for their reduced pathogenicity. However, it is unclear whether lung cell infection by BA.5, which displaced these variants, remains...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-06-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-023-39147-4 |
| _version_ | 1797801334654631936 |
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| author | Markus Hoffmann Lok-Yin Roy Wong Prerna Arora Lu Zhang Cheila Rocha Abby Odle Inga Nehlmeier Amy Kempf Anja Richter Nico Joel Halwe Jacob Schön Lorenz Ulrich Donata Hoffmann Martin Beer Christian Drosten Stanley Perlman Stefan Pöhlmann |
| author_facet | Markus Hoffmann Lok-Yin Roy Wong Prerna Arora Lu Zhang Cheila Rocha Abby Odle Inga Nehlmeier Amy Kempf Anja Richter Nico Joel Halwe Jacob Schön Lorenz Ulrich Donata Hoffmann Martin Beer Christian Drosten Stanley Perlman Stefan Pöhlmann |
| author_sort | Markus Hoffmann |
| collection | DOAJ |
| description | Abstract The SARS-CoV-2 Omicron subvariants BA.1 and BA.2 exhibit reduced lung cell infection relative to previously circulating SARS-CoV-2 variants, which may account for their reduced pathogenicity. However, it is unclear whether lung cell infection by BA.5, which displaced these variants, remains attenuated. Here, we show that the spike (S) protein of BA.5 exhibits increased cleavage at the S1/S2 site and drives cell-cell fusion and lung cell entry with higher efficiency than its counterparts from BA.1 and BA.2. Increased lung cell entry depends on mutation H69Δ/V70Δ and is associated with efficient replication of BA.5 in cultured lung cells. Further, BA.5 replicates in the lungs of female Balb/c mice and the nasal cavity of female ferrets with much higher efficiency than BA.1. These results suggest that BA.5 has acquired the ability to efficiently infect lung cells, a prerequisite for causing severe disease, suggesting that evolution of Omicron subvariants can result in partial loss of attenuation. |
| first_indexed | 2024-03-13T04:49:53Z |
| format | Article |
| id | doaj.art-d5890df25e6a47a4a0fb537c6e7a81a4 |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-13T04:49:53Z |
| publishDate | 2023-06-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-d5890df25e6a47a4a0fb537c6e7a81a42023-06-18T11:19:14ZengNature PortfolioNature Communications2041-17232023-06-0114111110.1038/s41467-023-39147-4Omicron subvariant BA.5 efficiently infects lung cellsMarkus Hoffmann0Lok-Yin Roy Wong1Prerna Arora2Lu Zhang3Cheila Rocha4Abby Odle5Inga Nehlmeier6Amy Kempf7Anja Richter8Nico Joel Halwe9Jacob Schön10Lorenz Ulrich11Donata Hoffmann12Martin Beer13Christian Drosten14Stanley Perlman15Stefan Pöhlmann16Infection Biology Unit, German Primate Center – Leibniz Institute for Primate ResearchDepartments of Microbiology and Immunology, BSB 3-712, University of IowaInfection Biology Unit, German Primate Center – Leibniz Institute for Primate ResearchInfection Biology Unit, German Primate Center – Leibniz Institute for Primate ResearchInfection Biology Unit, German Primate Center – Leibniz Institute for Primate ResearchDepartments of Microbiology and Immunology, BSB 3-712, University of IowaInfection Biology Unit, German Primate Center – Leibniz Institute for Primate ResearchInfection Biology Unit, German Primate Center – Leibniz Institute for Primate ResearchInstitute of Virology, Charité - Universitätsmedizin Berlin, Campus Charité MitteInstitut für Virusdiagnostik (IVD), Friedrich-Loeffler-InstitutInstitut für Virusdiagnostik (IVD), Friedrich-Loeffler-InstitutInstitut für Virusdiagnostik (IVD), Friedrich-Loeffler-InstitutInstitut für Virusdiagnostik (IVD), Friedrich-Loeffler-InstitutInstitut für Virusdiagnostik (IVD), Friedrich-Loeffler-InstitutInstitute of Virology, Charité - Universitätsmedizin Berlin, Campus Charité MitteDepartments of Microbiology and Immunology, BSB 3-712, University of IowaInfection Biology Unit, German Primate Center – Leibniz Institute for Primate ResearchAbstract The SARS-CoV-2 Omicron subvariants BA.1 and BA.2 exhibit reduced lung cell infection relative to previously circulating SARS-CoV-2 variants, which may account for their reduced pathogenicity. However, it is unclear whether lung cell infection by BA.5, which displaced these variants, remains attenuated. Here, we show that the spike (S) protein of BA.5 exhibits increased cleavage at the S1/S2 site and drives cell-cell fusion and lung cell entry with higher efficiency than its counterparts from BA.1 and BA.2. Increased lung cell entry depends on mutation H69Δ/V70Δ and is associated with efficient replication of BA.5 in cultured lung cells. Further, BA.5 replicates in the lungs of female Balb/c mice and the nasal cavity of female ferrets with much higher efficiency than BA.1. These results suggest that BA.5 has acquired the ability to efficiently infect lung cells, a prerequisite for causing severe disease, suggesting that evolution of Omicron subvariants can result in partial loss of attenuation.https://doi.org/10.1038/s41467-023-39147-4 |
| spellingShingle | Markus Hoffmann Lok-Yin Roy Wong Prerna Arora Lu Zhang Cheila Rocha Abby Odle Inga Nehlmeier Amy Kempf Anja Richter Nico Joel Halwe Jacob Schön Lorenz Ulrich Donata Hoffmann Martin Beer Christian Drosten Stanley Perlman Stefan Pöhlmann Omicron subvariant BA.5 efficiently infects lung cells Nature Communications |
| title | Omicron subvariant BA.5 efficiently infects lung cells |
| title_full | Omicron subvariant BA.5 efficiently infects lung cells |
| title_fullStr | Omicron subvariant BA.5 efficiently infects lung cells |
| title_full_unstemmed | Omicron subvariant BA.5 efficiently infects lung cells |
| title_short | Omicron subvariant BA.5 efficiently infects lung cells |
| title_sort | omicron subvariant ba 5 efficiently infects lung cells |
| url | https://doi.org/10.1038/s41467-023-39147-4 |
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