Signaling mechanisms of SARS-CoV-2 Nucleocapsid protein in viral infection, cell death and inflammation

• Published in: International journal of biological sciences Vol. 18; no. 12; pp. 4704 - 4713
• Main Authors: Wang, Wenbiao, Chen, Junzhe, Yu, Xueqing, Lan, Hui-Yao
• Format: Journal Article
• Language: English
• Published: Australia Ivyspring International Publisher Pty Ltd 01.01.2022; Ivyspring International Publisher
• Subjects: 14-3-3 protein; Acetylation; Adapters; Adaptive control; Adaptor proteins; Agglomeration; AKT protein; Amino acid sequence; Amino acids; Angiotensin; Animal models; Antibodies; Antiviral agents; Apoptosis; Assembly; Attenuation; Biological activity; Biology; Caspase-1; Cell cycle; Cell Death; Central nervous system diseases; Condensates; Coronaviridae; Coronaviruses; COVID-19; Cytokine Release Syndrome; Dengue fever; Disease transmission; Elongation; Epithelium; Fever; Gene silencing; Genomes; Health risks; Homology; Humans; Immune response; Immune system; Infections; Inflammation; Influenza A; Injuries; Kidneys; Life cycles; Liquid phases; Lungs; Membrane proteins; Membranes; Modulation; Mortality; Movement disorders; Nucleic acids; Nucleocapsids; Packaging; Pandemics; Pattern recognition; Peptidyl-dipeptidase A; Phase transitions; Pneumonia; Proteasomes; Protein denaturation; Protein synthesis; Proteins; Public health; Pyroptosis; Replication; Residues; Respiratory diseases; Respiratory distress syndrome; Review; RNA polymerase; RNA, Viral; RNA-binding protein; SARS-CoV-2; Severe acute respiratory syndrome; Severe acute respiratory syndrome coronavirus 2; Signs and symptoms; Translocation; Trends; Tumor necrosis factor-TNF; Vaccines; Vector-borne diseases; Vesicles; Viral diseases; Viral infections; Virology; Viruses; Hong Kong China; China
• ISSN: 1449-2288; 1449-2288
• DOI: 10.7150/ijbs.72663

COVID-19 which is caused by severe acute respiratory syndrome coronavirus (SARS-CoV-2) has posed a worldwide pandemic and a major global public health threat. SARS-CoV-2 Nucleocapsid (N) protein plays a critical role in multiple steps of the viral life cycle and participates in viral replication, transcription, and assembly. The primary roles of N protein are to assemble with genomic RNA into the viral RNA-protein (vRNP) complex and to localize to the replication transcription complexes (RTCs) to enhance viral replication and transcription. N protein can also undergo liquid-liquid phase separation (LLPS) with viral genome RNA and inhibit stress granules to facilitate viral replication and assembly. Besides the function in viral life cycle, N protein can bind GSDMD to antagonize pyroptosis but promotes cell death via the Smad3-dependent G1 cell cycle arrest mechanism. In innate immune system, N protein inhibits IFN-β production and RNAi pathway for virus survival. However, it can induce expression of proinflammatory cytokines by activating NF-κB signaling and NLRP3 inflammasome, resulting in cytokine storms. In this review article, we are focusing on the signaling mechanisms of SARS-CoV-2 N protein in viral replication, cell death and inflammation.