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bioRxiv · 10.1101/2021.06.17.448809

Astrovirus Disrupts Intestinal Barrier Function by Activating Epithelial-Mesenchymal Transition

Hargest, V.·Neale, G.·Schultz-Cherry, S.
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Abstract

Human astroviruses (HAstV), positive sense single-stranded RNA viruses, are one of the leading causes of diarrhea worldwide. Despite their high prevalence, the cellular mechanisms of astrovirus pathogenesis remain ill-defined. Previous studies showed HAstV increased epithelial barrier permeability by causing a relocalization of the tight junction protein, occludin. In these studies, we demonstrate that HAstV infection induces epithelial-mesenchymal transition (EMT), by upregulation the transcription of EMT-related genes within 8 hours post-infection (hpi), followed by the loss of cell-cell contacts and disruption of polarity by 24 hpi. Unlike the relocalization of tight junction proteins, HAstV-induced EMT requires productive replication and is independent of cellular factors including transforming growth factor-{beta} (TGF-{beta}). While multiple classical HAstV serotypes, including clinical isolates, induce EMT, the non-classical genotype HAstV-VA1 and two strains of reovirus are incapable of inducing EMT. This finding puts classical strains of HAstV-1 in an exclusive group of non-oncogenic viruses triggering EMT.

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Hargest, V., Neale, G., Schultz-Cherry, S.. 2021-06-17. Astrovirus Disrupts Intestinal Barrier Function by Activating Epithelial-Mesenchymal Transition. https://doi.org/10.1101/2021.06.17.448809

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