Table 1.
Specific viral antagonism mechanisms at each stage of interferon signaling
| Working model | Viral protein | Targets | Mechanisms | References |
|---|---|---|---|---|
| Evasion of PRRs recognition of viral RNA | NSP10 | viral RNA | cofactor of NSP16 for RNA cap methylation | Wilamowski et al.104, Viswanathan et al105 |
| NSP14 | viral RNA | guanine-N7-methyltransferase activity that can mimic 5′cap structure on the viral RNA | Ogando et al.106 | |
| NSP16 | viral RNA | 2′-O-methyltransferase activity involved in viral RNA capping | Wilamowski et al.104, Viswanathan et al.105 | |
| NSP15 | viral RNA | processes viral RNA and limits the formation of dsRNA intermediates | Deng et al.107 | |
| Inhibition of PRRs-mediated signaling cascades | N | TRIM25 | interferes with the interaction of TRIM25 and RIG-I | Wang et al.108, Zhao et al.109 |
| STAT1/STAT2 | suppresses phosphorylation and nuclear translocation of STAT1 and STAT2 | Mu et al.110 | ||
| M | MAVS | impairs MAVS aggregation and its recruitment of downstream TRAF3, TBK1, and IRF3 | Fu et al.111, Zheng et al.112 | |
| TBK1 | interacts with TBK1, thus preventing the formation of the multiprotein complex | Fu et al.111, Zheng et al. 112 | ||
| ORF9b | TOM70 | suppresses type I interferon (IFN-I) responses through association with TOM70 | Jiang et al.113 | |
| ORF3b | IRF3 | prevents the translocation of IRF3 into the nucleus | Konno et al.114 | |
| NSP13 | TBK1 | interacts with TBK1 and inhibits TKB1/IRF3 activation | Guo et al.115, Lei et al.116 | |
| NSP15 | IRF3 | interacts with RNF41, an E3 ligase associated with activation of IRF3 | Gordon et al.117 | |
| ORF3a | STAT1 | suppresses STAT1 phosphorylation via upregulating SOCS1 | Wang et al.118 | |
| NSP6 | TBK1 | binds TBK1 to suppress IRF3 phosphorylation | Xia et al.119 | |
| ORF6 | IRF3 | binds importin karyopherin α 2 (KPNA2) to inhibit IRF3 nuclear translocation | Miorin et al.120 | |
| STAT1 | binds directly to the Nup98-Rae1 complex to block STAT nuclear import | Miorin et al.120 | ||
| Modulation of ubiquitination and deubiquitination | N | RIG-I | associates with TRIM25 and suppresses the ubiquitination of RIG-I | Wang et al.108 |
| M | TBK1 | induces TBK1 degradation via K48-linked ubiquitination | Sui et al.121 | |
| PLpro | ISG15 | cleavage of ISG15 from IRF3 and attenuates type I interferon responses | Shin et al.122 | |
| mediates de-ISGyaltion of MDA5 and inhibit IFN response | Liu et al.123 | |||
| ORF9b | NEMO | interrupts K63-linked ubiquitination of NEMO | Wu et al.124 | |
| Viral proteases-mediated cleavage | PLpro | IRF3 | direct cleavage of IRF3 by NSP3 results in reduced type I IFN response | Moustaqil et al.125 |
| 3Clpro | NEMO | 3Clpro cleaves NEMO to induces the death of human brain endothelial cells | Josephine Lampe et al.126 | |
| Host translation shutoff | NSP1 | 40S subunit | shuts down host protein translation and subsequently blocks host immune functions | Zhang et al.127 |
| NSP14 | Unknown | exerts translational inhibition to abolish the IFN-I-dependent induction of ISGs | Hsu et al.128 | |
| NSP10 | NSP14 | cofactor of NSP14 Exerts translational inhibition to abolish the IFN-I-dependent induction of ISGs | Hsu et al.128 |