Abstract
Coronavirus accessory proteins are a unique set of proteins whose genes are interspersed among or within the genes encoding structural proteins. Different coronavirus genera, or even different species within the same coronavirus genus, encode varying amounts of accessory proteins, leading to genus- or species-specificity. Though accessory proteins are dispensable for the replication of coronavirus in vitro, they play important roles in regulating innate immunity, viral proliferation, and pathogenicity. The function of accessory proteins on virus infection and pathogenesis is an area of particular interest. In this review, we summarize the current knowledge on accessory proteins of several representative coronaviruses that infect humans or animals, including the emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), with an emphasis on their roles in interaction between virus and host, mainly involving stress response, innate immunity, autophagy, and apoptosis. The cross-talking among these pathways is also discussed.
Highlights
Coronavirus (CoV) infection usually causes mild respiratory symptoms, gastroenteritis, and hepatitis in humans and animals, but in some cases, it leads to life-threatening disease
We summarize current knowledge on the accessory proteins of several representative CoVs, including human and animal CoVs (SARS-CoVs, MERS-CoV, HCoV229E, HCoV-OC43, MHV, FIPV, porcine enteric diarrhea virus (PEDV), TGEV, infectious bronchitis virus (IBV), and porcine deltacoronavirus (PDCoV)), with particular emphasis on the association of interactions between virus and host
The recognition of PAMPs by cellular RNA sensor RIG-I/Melanoma differentiation gene 5 (MDA5) is the initial step, which was targeted by various accessory proteins via different strategies, such as sequestration of dsRNA recognition by MDA5 [38] and inhibition of interaction between double-stranded RNA-binding protein with RIG-I or MDA5 [39] by MERS-CoVNS4a protein, attenuation of dsRNA binding to RIG-I/MDA5 by PDCoV NS6 protein [40], and an unknown mechanism for MERS-CoV ORF8b [41]
Summary
Coronavirus (CoV) infection usually causes mild respiratory symptoms, gastroenteritis, and hepatitis in humans and animals, but in some cases, it leads to life-threatening disease. The α-CoVs and β-CoVs only infect mammals, including human CoVs (HCoV-229E, HCoV-OC43, SARS-CoVs, and MERS-CoV) and animal CoVs (mouse hepatitis virus (MHV), PEDV, feline infectious peritonitis virus (FIPV), porcine transmissible gastroenteritis virus (TGEV), swine acute diarrhea syndrome coronavirus (SADS-CoV)) [9,10,11]. We summarize current knowledge on the accessory proteins of several representative CoVs, including human and animal CoVs (SARS-CoVs, MERS-CoV, HCoV229E, HCoV-OC43, MHV, FIPV, PEDV, TGEV, IBV, and PDCoV), with particular emphasis on the association of interactions between virus and host (stress response, innate immunity, autophagy, and apoptosis). Kinase 2; JAK1, Janus kinase 1; STAT1/2, signal transducer and activator of transcription 1/2; IRF9, interferon regulatory factor 9; ISGF3, IFN-stimulated gene factor 3; OAS, oligoadenylate synthetase; PKR, protein kinase R; ISRE, IFN-stimulated response element; P, phosphate
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