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, Hans H. Wandall

*Corresponding author for this work

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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.

Original languageEnglish
Article number7000
JournalNature Communications
Volume14
Number of pages19
ISSN2041-1723
DOIs
Publication statusPublished - 2023

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