Identification of Host PDZ-Based Interactions with the SARS-CoV-2 E Protein in Human Monocytes
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Published:2023-08-14
Issue:16
Volume:24
Page:12793
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ISSN:1422-0067
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Container-title:International Journal of Molecular Sciences
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language:en
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Short-container-title:IJMS
Author:
Ávila-Flores Antonia1ORCID, Sánchez-Cabezón Juan José1, Ochoa-Echeverría Ane1, Checa Ana I.1, Rosas-García Jorge2, Téllez-Araiza Mariana2, Casado Sara1ORCID, Liébana Rosa1, Santos-Mendoza Teresa2ORCID, Mérida Isabel1ORCID
Affiliation:
1. Department of Immunology and Oncology, Spanish National Centre for Biotechnology, 28049 Madrid, Spain 2. Laboratory of Transcriptomics and Molecular Immunology, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Mexico City 14080, Mexico
Abstract
Proteins containing PDZ (post-synaptic density, PSD-95/disc large, Dlg/zonula occludens, ZO-1) domains assemble signaling complexes that orchestrate cell responses. Viral pathogens target host PDZ proteins by coding proteins containing a PDZ-binding motif (PBM). The presence of a PBM in the SARS-CoV-2 E protein contributes to the virus’s pathogenicity. SARS-CoV-2 infects epithelia, but also cells from the innate immune response, including monocytes and alveolar macrophages. This process is critical for alterations of the immune response that are related to the deaths caused by SARS-CoV-2. Identification of E-protein targets in immune cells might offer clues to understanding how SARS-CoV-2 alters the immune response. We analyzed the interactome of the SARS-CoV-2 E protein in human monocytes. The E protein was expressed fused to a GFP tag at the amino terminal in THP-1 monocytes, and associated proteins were identified using a proteomic approach. The E-protein interactome provided 372 partners; only 8 of these harbored PDZ domains, including the cell polarity protein ZO-2, the chemoattractant IL-16, and syntenin. We addressed the expression and localization of the identified PDZ proteins along the differentiation of primary and THP-1 monocytes towards macrophages and dendritic cells. Our data highlight the importance of identifying the functions of PDZ proteins in the maintenance of immune fitness and the viral alteration of inflammatory response.
Funder
European Commission—Next Generation EU Spanish Ministry of Science and Innovation Jesus Serra Foundation Mexican National Council of Science and Technology
Subject
Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis
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