Table 1. Evasion mechanisms of human respiratory viruses to type I interferon*.

Virus	Viral proteins interfering with interferon induction and signaling	Reference
Human rhinovirus	IFN induction: VPg interferes with viral RNA recognition by RNA sensors; 2A protease reduces cap-dependent translation of cellular mRNA; 2A and 3C proteases cleave MAVS. IFN signaling: 3C protease inhibits activation of antiviral protein complexes.	(5)
Human metapneumovirus	IFN induction: G interferes with TLR4 signaling; SH inhibits NF-κB signaling; M2.2 protein interferes with MAVS and inhibits IRF7 phosphorylation. IFN signaling: SH prevents STAT1 phosphorylation.	(6)
Respiratory syncytial virus	IFN induction: NS1 inhibits IRF3 phosphorylation, inhibits TRIM25-mediated RIG-I ubiquitination; NS2 binds to RIG-I and reduces IRF3 activation; G reduces IFN-λ production. IFN signaling: NS1 promotes OASL degradation and inhibits IFNAR1 expression; NS1 and NS2 induce STAT2 degradation.	(5)
Influenza virus	IFN induction: NS1 interferes with viral RNA sensing by TLR and RIG-I, binds to viral RNA and reduces RIG-I activation, inhibits TRIM25-mediated RIG-I ubiquitination and prevents the export of cellular mRNA to cytoplasm; PB1-F2 and PB2 interfere with MAVS; PA reduces IRF3 activation; M2 protein interacts with MAVS. IFN signaling: NS1 reduces PKR and OASL activation; HA induces IFNAR1 degradation; SOCS inhibits STAT2; NP and M2 protein interfere with PKR activation.	(7)
Severe acute respiratory syndrome coronavirus	IFN induction: NSP14 methylates capped RNA transcripts; NSP15 cleaves 5′-polyuridines from viral RNA; NSP16 and NSP10 methylate viral RNA cap; N protein inhibits TRIM25-mediated RIG-I ubiquitination; NSP3 deubiquitinates cellular substrates (possibly RIG-I) and inhibits IRF3 phosphorylation; ORF9b targets MAVS, TRAF3 and TRAF6 to degradation; M protein impedes TRAF3/TBK1/IKKε complex formation; ORF3b might target MAVS; NSP1 promotes cellular mRNA degradation and prevents host mRNA translation. IFN signaling: ORF3a promotes IFNAR1 degradation; NSP1 decreases STAT1 phosphorylation; ORF6 inhibits nuclear translocation of STAT1.	(8)

*G, glycoprotein; HA, hemagglutinin; IFN, interferon; IFNAR1, IFN-α/β receptor 1; IRF, IFN regulatory factor; M, matrix; MAVS, mitochondrial antiviral signaling protein; N, nucleocapsid; NP, nucleocapsid protein; NS, nonstructural; NSP, nonstructural protein, OASL, 2’-5′ oligoadenylate synthetase-ribonuclease L; ORF, open reading frame; PA, polymerase acidic; PB, polymerase basic; PKR, protein kinase receptor; RIG-I, retinoic acid‒inducible gene I; SH, viroporin protein; SOCS, suppressor of cytokine signaling; STAT, signal transducer and activator of transcription; TANK, TRAF family member‒associated NF-κB activator; TBK1, TANK binding kinase 1; TLR, Toll-like receptor; TRAF, tumor necrosis factor receptor‒associated factor; TRIM25, tripartite motif containing 25.