Protein Disulfide Isomerase A4 Is Involved in Genome Uncoating during Human Astrovirus Cell Entry.
Title | Protein Disulfide Isomerase A4 Is Involved in Genome Uncoating during Human Astrovirus Cell Entry. |
Publication Type | Journal Article |
Year of Publication | 2020 |
Authors | Aguilar-Hernández, Nayeli, Meyer Lena, López Susana, DuBois Rebecca M., and Arias Carlos F. |
Journal | Viruses |
Volume | 13 |
Issue | 1 |
Date Published | 2020 Dec 31 |
ISSN | 1999-4915 |
Keywords | Astroviridae Infections, Capsid Proteins, Cell Line, Cells, Cultured, Host-Pathogen Interactions, Humans, Mamastrovirus, Protein Binding, Protein Disulfide-Isomerases, Virus Internalization, Virus Uncoating |
Abstract | 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. |
DOI | 10.3390/v13010053 |
Alternate Journal | Viruses |
PubMed ID | 33396308 |
PubMed Central ID | PMC7824429 |
Grant List | R01AI144090 / NH / NIH HHS / United States |