Protein Disulfide Isomerase A4 Is Involved in Genome Uncoating during Human Astrovirus Cell Entry
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Departamento de Genética del Desarrollo y Fisiología Molecular, Instituto de Biotecnología, Universidad Nacional Autónoma de México, Cuernavaca CP 62210, Mexico
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Department of Biomolecular Engineering, University of California, Santa Cruz, CA 95064, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Susana Guix
Viruses 2021, 13(1), 53; https://doi.org/10.3390/v13010053
Received: 17 November 2020
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Revised: 18 December 2020
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Accepted: 21 December 2020
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Published: 31 December 2020
(This article belongs to the Special Issue Gastroenteritis Viruses)
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 Escherichia coli. 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.
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Keywords:
astrovirus; protein disulfide isomerase; virus entry
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MDPI and ACS Style
Aguilar-Hernández, N.; Meyer, L.; López, S.; DuBois, R.M.; Arias, C.F. Protein Disulfide Isomerase A4 Is Involved in Genome Uncoating during Human Astrovirus Cell Entry. Viruses 2021, 13, 53. https://doi.org/10.3390/v13010053
AMA Style
Aguilar-Hernández N, Meyer L, López S, DuBois RM, Arias CF. Protein Disulfide Isomerase A4 Is Involved in Genome Uncoating during Human Astrovirus Cell Entry. Viruses. 2021; 13(1):53. https://doi.org/10.3390/v13010053
Chicago/Turabian StyleAguilar-Hernández, Nayeli, Lena Meyer, Susana López, Rebecca M. DuBois, and Carlos F. Arias. 2021. "Protein Disulfide Isomerase A4 Is Involved in Genome Uncoating during Human Astrovirus Cell Entry" Viruses 13, no. 1: 53. https://doi.org/10.3390/v13010053
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