Glycoengineered keratinocyte library reveals essential functions of specific glycans for all stages of HSV-1 infection
Abstract Viral and host glycans represent an understudied aspect of host-pathogen interactions, despite potential implications for treatment of viral infections. This is due to lack of easily accessible tools for analyzing glycan function in a meaningful context. Here we generate a glycoengineered k...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-11-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-023-42669-6 |
| _version_ | 1827770450232475648 |
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| author | Ieva Bagdonaite Irina N. Marinova Asha M. Rudjord-Levann Emil M. H. Pallesen Sarah L. King-Smith Richard Karlsson Troels B. Rømer Yen-Hsi Chen Rebecca L. Miller Sigvard Olofsson Rickard Nordén Tomas Bergström Sally Dabelsteen Hans H. Wandall |
| author_facet | Ieva Bagdonaite Irina N. Marinova Asha M. Rudjord-Levann Emil M. H. Pallesen Sarah L. King-Smith Richard Karlsson Troels B. Rømer Yen-Hsi Chen Rebecca L. Miller Sigvard Olofsson Rickard Nordén Tomas Bergström Sally Dabelsteen Hans H. Wandall |
| author_sort | Ieva Bagdonaite |
| collection | DOAJ |
| description | Abstract Viral and host glycans represent an understudied aspect of host-pathogen interactions, despite potential implications for treatment of viral infections. This is due to lack of easily accessible tools for analyzing glycan function in a meaningful context. Here we generate a glycoengineered keratinocyte library delineating human glycosylation pathways to uncover roles of specific glycans at different stages of herpes simplex virus type 1 (HSV-1) infectious cycle. We show the importance of cellular glycosaminoglycans and glycosphingolipids for HSV-1 attachment, N-glycans for entry and spread, and O-glycans for propagation. While altered virion surface structures have minimal effects on the early interactions with wild type cells, mutation of specific O-glycosylation sites affects glycoprotein surface expression and function. In conclusion, the data demonstrates the importance of specific glycans in a clinically relevant human model of HSV-1 infection and highlights the utility of genetic engineering to elucidate the roles of specific viral and cellular carbohydrate structures. |
| first_indexed | 2024-03-11T12:39:43Z |
| format | Article |
| id | doaj.art-80ea0c4849164c8d9697a64b5796ebff |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-11T12:39:43Z |
| publishDate | 2023-11-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-80ea0c4849164c8d9697a64b5796ebff2023-11-05T12:22:03ZengNature PortfolioNature Communications2041-17232023-11-0114111910.1038/s41467-023-42669-6Glycoengineered keratinocyte library reveals essential functions of specific glycans for all stages of HSV-1 infectionIeva Bagdonaite0Irina N. Marinova1Asha M. Rudjord-Levann2Emil M. H. Pallesen3Sarah L. King-Smith4Richard Karlsson5Troels B. Rømer6Yen-Hsi Chen7Rebecca L. Miller8Sigvard Olofsson9Rickard Nordén10Tomas Bergström11Sally Dabelsteen12Hans H. Wandall13Copenhagen Center for Glycomics, Institute of Cellular and Molecular Medicine, University of CopenhagenCopenhagen Center for Glycomics, Institute of Cellular and Molecular Medicine, University of CopenhagenCopenhagen Center for Glycomics, Institute of Cellular and Molecular Medicine, University of CopenhagenCopenhagen Center for Glycomics, Institute of Cellular and Molecular Medicine, University of CopenhagenCopenhagen Center for Glycomics, Institute of Cellular and Molecular Medicine, University of CopenhagenCopenhagen Center for Glycomics, Institute of Cellular and Molecular Medicine, University of CopenhagenCopenhagen Center for Glycomics, Institute of Cellular and Molecular Medicine, University of CopenhagenCopenhagen Center for Glycomics, Institute of Cellular and Molecular Medicine, University of CopenhagenCopenhagen Center for Glycomics, Institute of Cellular and Molecular Medicine, University of CopenhagenDepartment of Infectious Diseases, Institute of Biomedicine, University of GothenburgDepartment of Infectious Diseases, Institute of Biomedicine, University of GothenburgDepartment of Infectious Diseases, Institute of Biomedicine, University of GothenburgDepartment of Odontology, University of CopenhagenCopenhagen Center for Glycomics, Institute of Cellular and Molecular Medicine, University of CopenhagenAbstract Viral and host glycans represent an understudied aspect of host-pathogen interactions, despite potential implications for treatment of viral infections. This is due to lack of easily accessible tools for analyzing glycan function in a meaningful context. Here we generate a glycoengineered keratinocyte library delineating human glycosylation pathways to uncover roles of specific glycans at different stages of herpes simplex virus type 1 (HSV-1) infectious cycle. We show the importance of cellular glycosaminoglycans and glycosphingolipids for HSV-1 attachment, N-glycans for entry and spread, and O-glycans for propagation. While altered virion surface structures have minimal effects on the early interactions with wild type cells, mutation of specific O-glycosylation sites affects glycoprotein surface expression and function. In conclusion, the data demonstrates the importance of specific glycans in a clinically relevant human model of HSV-1 infection and highlights the utility of genetic engineering to elucidate the roles of specific viral and cellular carbohydrate structures.https://doi.org/10.1038/s41467-023-42669-6 |
| spellingShingle | Ieva Bagdonaite Irina N. Marinova Asha M. Rudjord-Levann Emil M. H. Pallesen Sarah L. King-Smith Richard Karlsson Troels B. Rømer Yen-Hsi Chen Rebecca L. Miller Sigvard Olofsson Rickard Nordén Tomas Bergström Sally Dabelsteen Hans H. Wandall Glycoengineered keratinocyte library reveals essential functions of specific glycans for all stages of HSV-1 infection Nature Communications |
| title | Glycoengineered keratinocyte library reveals essential functions of specific glycans for all stages of HSV-1 infection |
| title_full | Glycoengineered keratinocyte library reveals essential functions of specific glycans for all stages of HSV-1 infection |
| title_fullStr | Glycoengineered keratinocyte library reveals essential functions of specific glycans for all stages of HSV-1 infection |
| title_full_unstemmed | Glycoengineered keratinocyte library reveals essential functions of specific glycans for all stages of HSV-1 infection |
| title_short | Glycoengineered keratinocyte library reveals essential functions of specific glycans for all stages of HSV-1 infection |
| title_sort | glycoengineered keratinocyte library reveals essential functions of specific glycans for all stages of hsv 1 infection |
| url | https://doi.org/10.1038/s41467-023-42669-6 |
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