Protein Disulfide Isomerase A4 Is Involved in Genome Uncoating during Human Astrovirus Cell Entry.

TitleProtein Disulfide Isomerase A4 Is Involved in Genome Uncoating during Human Astrovirus Cell Entry.
Publication TypeJournal Article
Year of Publication2020
AuthorsAguilar-Hernández, Nayeli, Meyer Lena, López Susana, DuBois Rebecca M., and Arias Carlos F.
Date Published2020 Dec 31
KeywordsAstroviridae Infections, Capsid Proteins, Cell Line, Cells, Cultured, Host-Pathogen Interactions, Humans, Mamastrovirus, Protein Binding, Protein Disulfide-Isomerases, Virus Internalization, Virus Uncoating

Although human astroviruses (HAstVs) are important agents of gastroenteritis in young children, the studies aimed at characterizing their biology have been limited, in particular regarding their cell entry process. It has been shown that HAstV serotype 8 enters human cells by a classical clathrin-mediated endocytosis pathway; however, the cell receptor or other cell entry factors that may be relevant for an efficient viral infection are unknown. In this work we used a far-Western blotting approach to identify cellular proteins that interact with the recombinant capsid spike proteins of HAstV serotypes 1, 2, and 8, synthesized in . We identified the 72 kDa protein disulfide isomerase A4 (PDIA4) as a binding partner for HAstV-1 and -8 spikes, but not for the HAstV-2 spike. In agreement with this observation, the PDI inhibitor 16F16 strongly blocked infection by HAstV serotypes 1 and 8, but not serotype 2. RNA interference of PDIA4 expression selectively blocked HAstV-8 infectivity. We also showed that the PDI activity does not affect virus binding or internalization but is required for uncoating of the viral genome.

Alternate JournalViruses
PubMed ID33396308
PubMed Central IDPMC7824429
Grant ListR01AI144090 / NH / NIH HHS / United States