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

Author

Listed:
  • 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)

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.

Suggested Citation

  • 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 & Ri, 2023. "Glycoengineered keratinocyte library reveals essential functions of specific glycans for all stages of HSV-1 infection," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-42669-6
    DOI: 10.1038/s41467-023-42669-6
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    References listed on IDEAS

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    1. Satvik R. Hadigal & Alex M. Agelidis & Ghadah A. Karasneh & Thessicar E. Antoine & Abraam M. Yakoub & Vishnu C. Ramani & Ali R. Djalilian & Ralph D. Sanderson & Deepak Shukla, 2015. "Heparanase is a host enzyme required for herpes simplex virus-1 release from cells," Nature Communications, Nature, vol. 6(1), pages 1-11, November.
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