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

Bagdonaite, I.; Marinova, I. N.; Rudjord-Levann, A. M.; Pallesen, E. M.; King-Smith, S.; Roemer, T. B.; Chen, Y.-H.; Dabelsteen, S.; Wandall, H. H.

doi:10.1101/2022.10.23.513399

bioRxiv · 10.1101/2022.10.23.513399

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

Bagdonaite, I.·Marinova, I. N.·Rudjord-Levann, A. M.·Pallesen, E. M.·King-Smith, S.·Roemer, T. B.·Chen, Y.-H.·Dabelsteen, S.·Wandall, H. H.

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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 generated 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 had minimal effects on the early interactions with wild type cells, mutation of specific O-glycosylation sites affected 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.

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Bagdonaite, I., Marinova, I. N., Rudjord-Levann, A. M., Pallesen, E. M., King-Smith, S., Roemer, T. B., Chen, Y.-H., Dabelsteen, S., Wandall, H. H.. 2022-10-23. Glycoengineered keratinocyte library reveals essential functions of specific glycans for all stages of HSV-1 life cycle. https://doi.org/10.1101/2022.10.23.513399

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