Identification of Host PDZ-Based Interactions with the SARS-CoV-2 E Protein in Human Monocytes.
IL-16
PDZ
SARS-CoV-2
ZO-2
envelope (E) protein
innate immune response
monocyte
syntenin
Journal
International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791
Informations de publication
Date de publication:
14 Aug 2023
14 Aug 2023
Historique:
received:
01
07
2023
revised:
01
08
2023
accepted:
06
08
2023
medline:
28
8
2023
pubmed:
26
8
2023
entrez:
26
8
2023
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 37628973
pii: ijms241612793
doi: 10.3390/ijms241612793
pmc: PMC10454406
pii:
doi:
Substances chimiques
Transcription Factors
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : European Commission to IM; Spanish Ministry of Science and Innovation (MINECO) to AAF and IM, the Jesus Serra Foundation to AAF; and the Mexican National Council of Science and Technology (CONACyT) to TSM.
ID : European Commission - Next Generation EU (Regulation EU 2020/2094) through CSIC's Global Health Platform (PTI Salud Global); and grants from the Spanish Ministry of Sciece; MINECO PID2019-108357RB-I00/10.13039/501100011033); CONACyT CB2015-250579.
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