Dissemin is shutting down on January 1st, 2025

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National Academy of Sciences, Proceedings of the National Academy of Sciences, 3(117), p. 1700-1710, 2020

DOI: 10.1073/pnas.1910138117

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Bile acids and ceramide overcome the entry restriction for GII.3 human norovirus replication in human intestinal enteroids

This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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Abstract

Significance Many viral pathogens replicate in the human small intestine where they must invade the epithelial barrier that has evolved to protect the host against microbial assaults. Using a human norovirus strain that requires bile to replicate in stem cell-derived human small intestinal enteroid cultures, we found that conjugated hydrophobic bile acids and ceramide are critical to allow virus entry and subsequent replication in jejunal enteroids. Glycochenodeoxycholic acid treatment of enteroids below the critical micellar concentration leads to multiple cellular responses, including rapid changes in endocytosis and exocytosis dynamics that the bile-requiring human norovirus deftly exploits to overcome the epithelial barrier. Our findings shed light on the role of bile acids and ceramide in human jejunal enterocytes that stimulate viral infection.