SARS-CoV-2 ORF3a-Mediated NF-κB Activation Is Not Dependent on TRAF-Binding Sequence.

Autor: Busscher BM; Department of Pathology, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA., Befekadu HB; Department of Physiology and Biophysics, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA., Liu Z; Department of Pathology, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA.; MOE Key Laboratory for Membraneless Organelles and Cellular Dynamics, Hefei National Research Center for Physical Sciences at the Microscale, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230027, China., Xiao TS; Department of Pathology, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA.
Jazyk: angličtina
Zdroj: Viruses [Viruses] 2023 Nov 08; Vol. 15 (11). Date of Electronic Publication: 2023 Nov 08.
DOI: 10.3390/v15112229
Abstrakt: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has caused a global pandemic of Coronavirus Disease 2019 (COVID-19). Excessive inflammation is a hallmark of severe COVID-19, and several proteins encoded in the SARS-CoV-2 genome are capable of stimulating inflammatory pathways. Among these, the accessory protein open reading frame 3a (ORF3a) has been implicated in COVID-19 pathology. Here we investigated the roles of ORF3a in binding to TNF receptor-associated factor (TRAF) proteins and inducing nuclear factor kappa B (NF-κB) activation. X-ray crystallography and a fluorescence polarization assay revealed low-affinity binding between an ORF3a N-terminal peptide and TRAFs, and a dual-luciferase assay demonstrated NF-κB activation by ORF3a. Nonetheless, mutation of the N-terminal TRAF-binding sequence PIQAS in ORF3a did not significantly diminish NF-κB activation in our assay. Our results thus suggest that the SARS-CoV-2 protein may activate NF-κB through alternative mechanisms.
Databáze: MEDLINE
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