Table 1 Coronavirus proteins that inhibit virus-induced interferon responses.
From: Type I and III interferon responses in SARS-CoV-2 infection
Mode of action | Protein | Virus | Function | Evasion mechanisms | Reference |
|---|---|---|---|---|---|
Evasion of sensing by host innate immune receptors | Nsp14 | SARS-CoV | Guanine-N7-methyltransferase | Modification of viral RNA and prevention of RIG-I-mediated viral sensing | |
Nsp15 | SARS-CoV | Endonuclease | Cleavage of viral RNA and prevention of viral sensing | ||
Nsp16 | SARS-CoV | 2′-O-methyl-transferase | Modification of viral RNA and prevention of MDA-5-mediated viral sensing | ||
Inhibition of innate immune receptor signaling and IFN production | Nsp1 | SARS-CoV, SARS-CoV-2 | Binding to small ribosomal subunit | Shutdown of host mRNA translation, including mRNAs for IFNs and ISGs | |
| Â | ? | Inhibition of IRF3 dimerization (SARS-CoV) | |||
Nsp3 | SARS-CoV, SARS-CoV-2 | Papain-like protease; deubiquitinating and deISGylating activity | Removal of K63-linked ubiquitin chains from TRAF3 and TRAF6 (SARS-CoV) and detachment of ISG15 from IRF3 (SARS-CoV-2) | ||
N | SARS-CoV, MERS-CoV | Binding to TRIM25 | Inhibition of TRIM25-mediated RIG-I ubiquitination and activation | ||
M | SARS-CoV | Association with RIG-I, TRAF3, TBK1, and IKKε | Prevention of the TBK1/IKKε-dependent activation of IRF3/IRF7 | ||
ORF3b | SARS-CoV, SARS-CoV-2 | ? | Inhibition of IRF3 nuclear translocation | ||
OFR6 | SARS-CoV, SARS-CoV-2 | Binding to karyopherin α2 and karyopherin β1 (?) | Inhibition of IRF3 nuclear translocation | ||
ORF9b | SARS-CoV, SARS-CoV-2 | Association with MAVS and TOM70 in mitochondria | AIP4-mediated degradation of MAVS, TRAF3, and TRAF6 (SARS-CoV) | ||
NS4b | MERS-CoV | Phosphodiesterase | Inhibition of type I and III IFN production | ||
Inhibition of IFNAR signaling and ISG expression | Nsp1 | SARS-CoV, SARS-CoV-2 | ? | Inhibition of STAT1 phosphorylation (SARS-CoV) | |
| Â | Binding to small ribosomal subunit | Shutdown of host mRNA translation, including mRNAs for IFNs and ISGs | |||
Nsp7 | SARS-CoV-2 | Binding to SRP | Inhibition of host protein secretion, including that of IFNs and ISGs | ||
Nsp9 | SARS-CoV-2 | Binding to SRP | Inhibition of host protein secretion, including that of IFNs and ISGs | ||
Nsp16 | SARS-CoV-2 | Binding to spliceosome components | Disruption of pre-mRNA splicing and the resulting inhibition of host protein expression, including that of ISGs | ||
ORF3a | SARS-CoV | ? | Degradation of IFNAR1 | ||
ORF3b | SARS-CoV | ? | Inhibition of ISRE activation and ISG expression | ||
ORF6 | SARS-CoV, SARS-CoV-2 | Binding to karyopherin α2 and karyopherin β1 | Disruption of the nuclear import complex and inhibition of STAT1 nuclear translocation | ||
N | SARS-CoV-2 | ? | Inhibition of STAT1/STAT2 phosphorylation | ||
Suppression of ISG function | NS4b | MERS-CoV | Phosphodiesterase | Degradation of 2′,5′-polyandenylates and inhibition of OAS/RNase L activity |
