Table 1.
Interferon Antagonistic Functions of Viral Proteins
| Protein | Target/mechanism | Virus | Citation |
|---|---|---|---|
| Nonstructural | |||
| NSP1 | Inhibition of mRNA export; binding of 40S ribosomal subunit | SARS-CoV-1; SARS-CoV-2; MERS-CoV; hCoV-NL63; hCoV-OC43; MHV | Lei and others (2013); Lokugamage and others (2015); Wang and others (2010); Schubert and others (2020); Zhang and others (2021) |
| NSP3 | Deubiquitylation of RIG-I; deubiquitylation of STING; deubiquitylation and DeISGylation of MDA5 | SARS-CoV-1; SARS-CoV-2; MERS-CoV; HCoV-NL63; MHV, PEDV | Clementz and others (2010); Xing and others (2013); Mielech and others (2014); Klemm and others (2020); Shin and others (2020) |
| NSP6 | Interaction with TBK1 prevents IRF3 phosphorylation | SARS-CoV-2 | Xia and others (2020) |
| NSP8 | Prevention of MDA5 polyubiquitylation | SARS-CoV-2 | Yang and others (2020b) |
| NSP12 | Inhibition of IRF3 nuclear translocation | SARS-CoV-2 | Wang and others (2021) |
| NSP13 | Interaction with TBK1 prevents TBK1 phosphorylation | SARS-CoV-2 | Xia and others (2020); Yuen and others (2020) |
| NSP14 | Capping of viral RNAs | SARS-CoV-2 | Chen and others (2009); Yuen and others (2020) |
| NSP15 | Degradation of viral dsRNA | SARS-CoV-2; MHV | Deng and others (2017); Yuen and others (2020) |
| NSP16 | Capping of viral RNA | SARS-CoV-1; SARS-CoV-2; MERS-CoV; MHV | Daffis and others (2010); Menachery and others (2014); Menachery and others (2017) |
| Structural | |||
| M | Disruption of TBK1-dependent IRF3 phosphorylation | SARS-CoV-1; SARS-CoV-2; MERS-CoV | Siu and others (2009); Lui and others (2016); Zheng and others (2020) |
| N | Shielding of viral RNA; inhibition of TRIM25-dependent RIG-I ubiquitylation | SARS-CoV-1; SARS-CoV-2; MERS-CoV | Kopecky-Bromberg and others (2007); Lu and others (2011); Lei and others (2020) |
| Accessory | |||
| ORF3b | Block of IRF3 phosphorylation | SARS-CoV-1; SARS-CoV-2 | Kopecky-Bromberg and others (2007); Konno and others (2020) |
| ORF4a | RNA-dependent sequestration of PACT (RLR cofactor); sequestration of dsRNA to prevent PKR activation | MERS-CoV | Almazan and others (2013); Yang and others (2013); Siu and others (2014); Rabouw and others (2016); Comar and others (2019) |
| ORF4b | Degradation of 2′,5′-oligoadenylate prevents RNaseL activation; disruption of MAVS interaction with TBK1/IKKe | MERS-CoV | Yang and others (2015); Thornbrough and others (2016); Comar and others (2019); Li and others (2021) |
| ORF6 | Inhibition of IRF3 nuclear translocation | SARS-CoV-1; SARS-CoV-2 | Frieman and others (2007); Kopecky-Bromberg and others (2007); Xia and others (2020); Yuen and others (2020) |
| ORF8(a/b) | Ubiquitin-dependent degradation of IRF3 | SARS-CoV-1 | Wong and others (2018) |
| ORF8b | Inhibition of HSP70-dependent activation of IKKe | MERS-CoV | Wong and others (2020) |
| ORF9b | Ubiquitin-dependent degradation of MAVS | SARS-CoV-1 | Shi and others (2014) |
| NS2 | Degradation of 2′,5′-oligoadenylate prevents RNaseL activation | HCoV-OC43; MHV; ECoV; BEV | Zhao and others (2012); Goldstein and others (2017) |
dsRNA, double-stranded RNA; hCoV, human coronavirus; IRF3, interferon regulatory transcription factor 3; M, membrane; MAVS, mitochondrial antiviral-signaling protein; MDA5, melanoma differentiation-associated gene 5; MERS-CoV, Middle East respiratory syndrome coronavirus; MHV, mouse hepatitis virus; mRNA, messenger RNA; N, nucleocapsid protein; NSP, nonstructural protein; ORF, open reading frame; PEDV, porcine epidemic diarrhea virus; PKR, protein kinase R; RIG-I, retinoic acid-associated gene-I; RLR, retinoic acid-associated gene-I (RIG-I)-like receptor; SARS-CoV, severe acute respiratory syndrome coronavirus.