Glycoengineered keratinocyte library reveals essential functions of specific glycans for all stages of HSV-1 infection

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 and Hans H. Wandall ()
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Ieva Bagdonaite: University of Copenhagen
Irina N. Marinova: University of Copenhagen
Asha M. Rudjord-Levann: University of Copenhagen
Emil M. H. Pallesen: University of Copenhagen
Sarah L. King-Smith: University of Copenhagen
Richard Karlsson: University of Copenhagen
Troels B. Rømer: University of Copenhagen
Yen-Hsi Chen: University of Copenhagen
Rebecca L. Miller: University of Copenhagen
Sigvard Olofsson: University of Gothenburg
Rickard Nordén: University of Gothenburg
Tomas Bergström: University of Gothenburg
Sally Dabelsteen: University of Copenhagen
Hans H. Wandall: University of Copenhagen

Nature Communications, 2023, vol. 14, issue 1, 1-19

Abstract: 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.

Date: 2023
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-42669-6

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DOI: 10.1038/s41467-023-42669-6

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