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Sphingolipid biosynthesis induces a conformational change in the murine norovirus receptor and facilitates viral infection

Cellular susceptibility to viral infections is in part determined by the presence of a host cellular receptor. Here we use murine norovirus as a model to uncover an unappreciated connection between an intracellular lipid biosynthetic enzyme and a receptor conformation permissive for viral infection....

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Autores principales: Orchard, Robert C., Wilen, Craig B., Virgin, Herbert W.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6158067/
https://www.ncbi.nlm.nih.gov/pubmed/30127493
http://dx.doi.org/10.1038/s41564-018-0221-8
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author Orchard, Robert C.
Wilen, Craig B.
Virgin, Herbert W.
author_facet Orchard, Robert C.
Wilen, Craig B.
Virgin, Herbert W.
author_sort Orchard, Robert C.
collection PubMed
description Cellular susceptibility to viral infections is in part determined by the presence of a host cellular receptor. Here we use murine norovirus as a model to uncover an unappreciated connection between an intracellular lipid biosynthetic enzyme and a receptor conformation permissive for viral infection. The serine palmitoyltransferase (SPT) complex is required for de novo sphingolipid biosynthesis and we find that its absence impairs the ability of murine norovirus to bind and enter cells. While, the SPT complex is dispensable for the surface expression of the norovirus receptor, CD300lf, SPT activity is required for CD300lf to adopt a conformation permissive for viral binding. Addition of extracellular ceramide to SPT deficient cells chemically complements both the conformational changes of CD300lf and the cellular susceptibility to murine norovirus infection. Taken together, these data indicate that intracellular sphingolipid biosynthesis regulates the conformation of the murine norovirus receptor, and therefore the tropism of murine norovirus. This indicates that intracellular biosynthetic pathways can regulate viral tropism even when the receptor for a virus is expressed on the target cell surface.
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spelling pubmed-61580672019-02-20 Sphingolipid biosynthesis induces a conformational change in the murine norovirus receptor and facilitates viral infection Orchard, Robert C. Wilen, Craig B. Virgin, Herbert W. Nat Microbiol Article Cellular susceptibility to viral infections is in part determined by the presence of a host cellular receptor. Here we use murine norovirus as a model to uncover an unappreciated connection between an intracellular lipid biosynthetic enzyme and a receptor conformation permissive for viral infection. The serine palmitoyltransferase (SPT) complex is required for de novo sphingolipid biosynthesis and we find that its absence impairs the ability of murine norovirus to bind and enter cells. While, the SPT complex is dispensable for the surface expression of the norovirus receptor, CD300lf, SPT activity is required for CD300lf to adopt a conformation permissive for viral binding. Addition of extracellular ceramide to SPT deficient cells chemically complements both the conformational changes of CD300lf and the cellular susceptibility to murine norovirus infection. Taken together, these data indicate that intracellular sphingolipid biosynthesis regulates the conformation of the murine norovirus receptor, and therefore the tropism of murine norovirus. This indicates that intracellular biosynthetic pathways can regulate viral tropism even when the receptor for a virus is expressed on the target cell surface. 2018-08-20 2018-10 /pmc/articles/PMC6158067/ /pubmed/30127493 http://dx.doi.org/10.1038/s41564-018-0221-8 Text en Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Orchard, Robert C.
Wilen, Craig B.
Virgin, Herbert W.
Sphingolipid biosynthesis induces a conformational change in the murine norovirus receptor and facilitates viral infection
title Sphingolipid biosynthesis induces a conformational change in the murine norovirus receptor and facilitates viral infection
title_full Sphingolipid biosynthesis induces a conformational change in the murine norovirus receptor and facilitates viral infection
title_fullStr Sphingolipid biosynthesis induces a conformational change in the murine norovirus receptor and facilitates viral infection
title_full_unstemmed Sphingolipid biosynthesis induces a conformational change in the murine norovirus receptor and facilitates viral infection
title_short Sphingolipid biosynthesis induces a conformational change in the murine norovirus receptor and facilitates viral infection
title_sort sphingolipid biosynthesis induces a conformational change in the murine norovirus receptor and facilitates viral infection
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6158067/
https://www.ncbi.nlm.nih.gov/pubmed/30127493
http://dx.doi.org/10.1038/s41564-018-0221-8
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