Abstract
A weak production of INF-β along with an exacerbated release of pro-inflammatory cytokines have been reported during infection by the novel SARS-CoV-2 virus. SARS-CoV-2 encodes several proteins able to counteract the host immune system, which is believed to be one of the most important features contributing to the viral pathogenesis and development of a severe clinical picture. Previous reports have demonstrated that SARS-CoV-2 N protein, along with some non-structural and accessory proteins, efficiently suppresses INF-β production by interacting with RIG-I, an important pattern recognition receptor (PRR) involved in the recognition of pathogen-derived molecules. In the present study, we better characterized the mechanism by which the SARS-CoV-2 N counteracts INF-β secretion and affects RIG-I signaling pathways. In detail, when the N protein was ectopically expressed, we noted a marked decrease in TRIM25-mediated RIG-I activation. The capability of the N protein to bind to, and probably mask, TRIM25 could be the consequence of its antagonistic activity. Furthermore, this interaction occurred at the SPRY domain of TRIM25, harboring the RNA-binding activity necessary for TRIM25 self-activation. Here, we describe new findings regarding the interplay between SARS-CoV-2 and the IFN system, filling some gaps for a better understanding of the molecular mechanisms affecting the innate immune response in COVID-19.
Highlights
Coronaviruses (CoVs) are a large family of single-stranded, positive-sense RNA viruses that belong to the family Coronaviridae [1,2]
We confirmed that SARS-CoV-2 N protein was able to block IFN-β promoter activation in a highly specific manner by inhibiting retinoic-acid inducible gene-I (RIG-I), but not melanoma differentiation-associated protein 5 (MDA-5), upon poly(I:C) stimulation
We evaluated the specific activity of the N protein on Riplet, another E3 ubiquitin ligase involved in the control of RIG-I functions
Summary
Coronaviruses (CoVs) are a large family of single-stranded, positive-sense RNA viruses that belong to the family Coronaviridae [1,2]. Coronavirus has a large RNA genome consisting of the open reading frames (ORFs) 1a and 1b encoding for two polyproteins which are proteolytically cleaved into 16 nonstructural proteins (nsp1–16) that play pivotal roles in the life cycle of CoVs [3,4,5,6]. Coronaviruses can infect humans and animals (bats, mice and birds) [7,8]; among them, CoV-229E, CoV-OC43, CoV-NL63, CoV-HKU1, SARS-CoV and MERS-CoV have been associated with human diseases [7,8,9,10]. SARS-CoV and MERS-CoV caused severe respiratory illness during the
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
