Conserved role of spike S2 domain N-glycosylation across betacoronaviruses
Abstract Besides acting as an immunological shield, the N-glycans of SARS-CoV-2 are also critical for viral life cycle. As the S2 subunit of spike is highly conserved across betacoronaviruses, we determined the functional significance of the five ‘stem N-glycans’ located in S2 between N1098-N1194. S...
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| Format: | Article |
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Nature Portfolio
2025-01-01
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| Series: | npj Viruses |
| Online Access: | https://doi.org/10.1038/s44298-024-00085-7 |
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| author | Qi Yang Anju Kelkar Balaji Manicassamy Sriram Neelamegham |
| author_facet | Qi Yang Anju Kelkar Balaji Manicassamy Sriram Neelamegham |
| author_sort | Qi Yang |
| collection | DOAJ |
| description | Abstract Besides acting as an immunological shield, the N-glycans of SARS-CoV-2 are also critical for viral life cycle. As the S2 subunit of spike is highly conserved across betacoronaviruses, we determined the functional significance of the five ‘stem N-glycans’ located in S2 between N1098-N1194. Studies were performed with 31 Asn-to-Gln mutants, betacoronavirus virus-like particles and single-cycle viral replicons. Deletions of stem N-glycans enhanced S1 shedding from trimeric spike, reduced ACE2 binding and abolished syncytia formation. When three or more N-glycans were deleted, spike expression on cell surface and incorporation into virions was both reduced. Viral entry function was progressively lost upon deleting the N1098 glycan in combination with additional glycosite modifications. In addition to SARS-CoV-2, deleting stem N-glycans in SARS-CoV and MERS-CoV spike also prevented viral entry into target cells. These data suggest multiple functional roles for the stem N-glycans, and evolutionarily conserved properties for these complex carbohydrates across human betacoronaviruses. |
| format | Article |
| id | doaj-art-a7f791113284478c83d7101814d4481d |
| institution | Kabale University |
| issn | 2948-1767 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Viruses |
| spelling | doaj-art-a7f791113284478c83d7101814d4481d2025-01-26T12:18:58ZengNature Portfolionpj Viruses2948-17672025-01-013111110.1038/s44298-024-00085-7Conserved role of spike S2 domain N-glycosylation across betacoronavirusesQi Yang0Anju Kelkar1Balaji Manicassamy2Sriram Neelamegham3Chemical & Biological Engineering, State University of New YorkChemical & Biological Engineering, State University of New YorkMicrobiology and Immunology, University of IowaChemical & Biological Engineering, State University of New YorkAbstract Besides acting as an immunological shield, the N-glycans of SARS-CoV-2 are also critical for viral life cycle. As the S2 subunit of spike is highly conserved across betacoronaviruses, we determined the functional significance of the five ‘stem N-glycans’ located in S2 between N1098-N1194. Studies were performed with 31 Asn-to-Gln mutants, betacoronavirus virus-like particles and single-cycle viral replicons. Deletions of stem N-glycans enhanced S1 shedding from trimeric spike, reduced ACE2 binding and abolished syncytia formation. When three or more N-glycans were deleted, spike expression on cell surface and incorporation into virions was both reduced. Viral entry function was progressively lost upon deleting the N1098 glycan in combination with additional glycosite modifications. In addition to SARS-CoV-2, deleting stem N-glycans in SARS-CoV and MERS-CoV spike also prevented viral entry into target cells. These data suggest multiple functional roles for the stem N-glycans, and evolutionarily conserved properties for these complex carbohydrates across human betacoronaviruses.https://doi.org/10.1038/s44298-024-00085-7 |
| spellingShingle | Qi Yang Anju Kelkar Balaji Manicassamy Sriram Neelamegham Conserved role of spike S2 domain N-glycosylation across betacoronaviruses npj Viruses |
| title | Conserved role of spike S2 domain N-glycosylation across betacoronaviruses |
| title_full | Conserved role of spike S2 domain N-glycosylation across betacoronaviruses |
| title_fullStr | Conserved role of spike S2 domain N-glycosylation across betacoronaviruses |
| title_full_unstemmed | Conserved role of spike S2 domain N-glycosylation across betacoronaviruses |
| title_short | Conserved role of spike S2 domain N-glycosylation across betacoronaviruses |
| title_sort | conserved role of spike s2 domain n glycosylation across betacoronaviruses |
| url | https://doi.org/10.1038/s44298-024-00085-7 |
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