Modeling of host PDZ-dependent interactions with SARS-CoV-2 envelope protein and changes in PDZ protein expression in macrophages and dendritic cells.

Autor:	Rosas-García J; Laboratory of Transcriptomics and Molecular Immunology, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Calzada de Tlalpan 4502, 14080, Mexico City, Mexico., Padilla-Zúñiga AJ; Department of Chemistry, Universidad Autónoma Metropolitana - Iztapalapa, Avenida San Rafael Atlixco 186, 09340, Mexico City, Mexico., Ávila-Flores A; Department of Immunology and Oncology, Spanish National Centre for Biotechnology, Darwin 3, 28049, Madrid, Spain., Gutiérrez-González LH; Laboratory of Transcriptomics and Molecular Immunology, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Calzada de Tlalpan 4502, 14080, Mexico City, Mexico., Mérida I; Department of Immunology and Oncology, Spanish National Centre for Biotechnology, Darwin 3, 28049, Madrid, Spain., Santos-Mendoza T; Laboratory of Transcriptomics and Molecular Immunology, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Calzada de Tlalpan 4502, 14080, Mexico City, Mexico.
Jazyk:	angličtina
Zdroj:	Journal of leukocyte biology [J Leukoc Biol] 2024 Nov 04; Vol. 116 (5), pp. 995-1006.
DOI:	10.1093/jleuko/qiae118
Abstrakt:	PDZ (PSD-95 [postsynaptic density protein 95]/Dlg [Discs large]/ZO-1 [zonula occludens-1]) domain-containing proteins constitute a large family of scaffolds involved in a wide range of cellular tasks and are mainly studied in polarity functions. Diverse host PDZ proteins can be targeted by viral pathogens that express proteins containing PDZ-binding motifs (PDZbms). Previously, we have identified host PDZ-based interactions with the SARS-CoV-2 E protein (2E) in human monocytes. Here, we deepen the study of these interactions by docking and molecular dynamics analyses to identify the most favorable PDZ-PDZbm interaction of 7 host PDZ proteins with the PDZbm of 2E. In addition, we analyzed changes in the expression of 3 of the PDZ proteins identified as 2E interactors in monocytes (syntenin, ZO-2, and interleukin-16), in human monocyte-derived macrophages and in dendritic cells upon stimulation. Our results suggest that these PDZ proteins may have important functions in professional antigen-presenting cells, and their targeting by the PDZbm of 2E, a central virulence determinant of SARS-CoV-2, supports the hypothesis that such PDZ-dependent interaction in immune cells may constitute a viral evasion mechanism. An inhibitor design based on the PDZbm of 2E in the development of drugs against a variety of diseases is discussed. Competing Interests: Conflicts of interest. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (© The Author(s) 2024. Published by Oxford University Press on behalf of Society for Leukocyte Biology.)
Databáze:	MEDLINE
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