ABSTRACT
A weak production of INF-ß 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-ß 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-ß 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.
Subject(s)
COVID-19/immunology , Coronavirus Nucleocapsid Proteins/immunology , DEAD Box Protein 58/immunology , Receptors, Immunologic/immunology , SARS-CoV-2/immunology , Transcription Factors/immunology , Tripartite Motif Proteins/immunology , Ubiquitin-Protein Ligases/immunology , COVID-19/genetics , COVID-19/virology , Coronavirus Nucleocapsid Proteins/genetics , DEAD Box Protein 58/genetics , Gene Expression Regulation , Host-Pathogen Interactions , Humans , Immunity, Innate , Interferon-beta/genetics , Interferon-beta/immunology , Promoter Regions, Genetic , Receptors, Immunologic/genetics , SARS-CoV-2/genetics , Signal Transduction , Transcription Factors/genetics , Tripartite Motif Proteins/genetics , Ubiquitin-Protein Ligases/geneticsABSTRACT
INTRODUCTION: The tripartite motif (TRIM) plays various roles in pathological and physiological functions, including neurological diseases, genetic disorders, carcinogenesis, innate immune signaling, and antiviral activity. TRIM56 is a cytoplasmic protein whose expression is stimulated by type I interferon and may function as an antiviral agent. Here, the authors conducted a systematic search on papers that reported antiviral effects of TRIM56. AREAS COVERED: The authors conducted a comprehensive search of the PubMed database without time or language limitation, after using the Medical Subject Headings (MeSH) Database terms. Initially, a structured search and full article review yielded 31 papers. Relevant original and review articles on TRIM56 were included. The reference lists were then reviewed, and the cited articles were added. Expert opinion: TRIM56 has been shown to have direct antiviral actions against positive-sense single-stranded RNA viruses from the families Flaviviridae, Coronaviridae, and Retroviridae. Moreover, it may be effective against negative-sense single-strand RNA viruses from the families Paramyxoviridae and Orthomyxoviridae, as well as a DNA virus, Herpes simplex virus 1 (HSV-1). These studies could suggest the potential of a TRIM56-based antiviral against COVID-19 from the family Coronaviridae, containing single-stranded positive-sense RNA genome. However, its efficacy and antiviral mechanisms need to be further examined.