학술논문
Glycoengineered keratinocyte library reveals essential functions of specific glycans for all stages of HSV-1 infection.
Document Type
Academic Journal
Author
Bagdonaite I; Copenhagen Center for Glycomics, Institute of Cellular and Molecular Medicine, University of Copenhagen, DK-2200, Copenhagen, Denmark. ieva@sund.ku.dk.; Marinova IN; Copenhagen Center for Glycomics, Institute of Cellular and Molecular Medicine, University of Copenhagen, DK-2200, Copenhagen, Denmark.; Rudjord-Levann AM; Copenhagen Center for Glycomics, Institute of Cellular and Molecular Medicine, University of Copenhagen, DK-2200, Copenhagen, Denmark.; Pallesen EMH; Copenhagen Center for Glycomics, Institute of Cellular and Molecular Medicine, University of Copenhagen, DK-2200, Copenhagen, Denmark.; King-Smith SL; Copenhagen Center for Glycomics, Institute of Cellular and Molecular Medicine, University of Copenhagen, DK-2200, Copenhagen, Denmark.; Karlsson R; Copenhagen Center for Glycomics, Institute of Cellular and Molecular Medicine, University of Copenhagen, DK-2200, Copenhagen, Denmark.; Rømer TB; Copenhagen Center for Glycomics, Institute of Cellular and Molecular Medicine, University of Copenhagen, DK-2200, Copenhagen, Denmark.; Chen YH; Copenhagen Center for Glycomics, Institute of Cellular and Molecular Medicine, University of Copenhagen, DK-2200, Copenhagen, Denmark.; Miller RL; Copenhagen Center for Glycomics, Institute of Cellular and Molecular Medicine, University of Copenhagen, DK-2200, Copenhagen, Denmark.; Olofsson S; Department of Infectious Diseases, Institute of Biomedicine, University of Gothenburg, SE-41346, Gothenburg, Sweden.; Nordén R; Department of Infectious Diseases, Institute of Biomedicine, University of Gothenburg, SE-41346, Gothenburg, Sweden.; Bergström T; Department of Infectious Diseases, Institute of Biomedicine, University of Gothenburg, SE-41346, Gothenburg, Sweden.; Dabelsteen S; Department of Odontology, University of Copenhagen, DK-2200, Copenhagen, Denmark.; Wandall HH; Copenhagen Center for Glycomics, Institute of Cellular and Molecular Medicine, University of Copenhagen, DK-2200, Copenhagen, Denmark. hhw@sund.ku.dk.
Source
Publisher: Nature Pub. Group Country of Publication: England NLM ID: 101528555 Publication Model: Electronic Cited Medium: Internet ISSN: 2041-1723 (Electronic) Linking ISSN: 20411723 NLM ISO Abbreviation: Nat Commun Subsets: MEDLINE
Subject
Language
English
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.
(© 2023. The Author(s).)
(© 2023. The Author(s).)