Glycoengineered keratinocyte library reveals essential functions of specific glycans for all stages of HSV-1 infection
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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.
| Originalsprog | Engelsk |
|---|---|
| Artikelnummer | 7000 |
| Tidsskrift | Nature Communications |
| Vol/bind | 14 |
| Antal sider | 19 |
| ISSN | 2041-1723 |
| DOI | |
| Status | Udgivet - 2023 |
Bibliografisk note
Funding Information:
We thank Karin Uch Hansen for technical assistance. We acknowledge the Core Facility for Integrated Microscopy, Faculty of Health and Medical Sciences, University of Copenhagen. We kindly thank Prashant Desai, Zene Matsuda, Gabriella Campadelli-Fiume, and Richard Longnecker for sharing virus strains, plasmids, and cell lines. We also thank Gary Cohen and Doina Atanasiu for their valuable guidance. This work was supported by Lundbeck Foundation (R219-2016-545, IB), Danish National Research Foundation (DNRF107) and European Comission (GlycoSkin H2020-ERC, HHW).
Funding Information:
We thank Karin Uch Hansen for technical assistance. We acknowledge the Core Facility for Integrated Microscopy, Faculty of Health and Medical Sciences, University of Copenhagen. We kindly thank Prashant Desai, Zene Matsuda, Gabriella Campadelli-Fiume, and Richard Longnecker for sharing virus strains, plasmids, and cell lines. We also thank Gary Cohen and Doina Atanasiu for their valuable guidance. This work was supported by Lundbeck Foundation (R219-2016-545, IB), Danish National Research Foundation (DNRF107) and European Comission (GlycoSkin H2020-ERC, HHW).
Publisher Copyright:
© 2023, The Author(s).
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