TABLE 1

Viral-mediated inhibition of protein kinase R (PKR) activity

Virus(es)Viral proteinMode of PKR inhibitionReferences
ssRNA
 OrthomyxoviridaeInfluenza ANS1Direct interaction/dsRNA-mediated interaction[26, 45]
Influenza B
 CoronaviridaeInfectious bronchitis virusNSp2Inhibition of phosphorylation[21]
hCoV-229aNSp15dsRNA sequestration[22]
MERS-CoVNS4adsRNA sequestration[23, 27]
 BunyaviridaeRift Valley fever virusNSsProteasome-mediated degradation[28]
 FiloviridaeEbolavirusVP35Unknown/possible dsRNA sequestration[29]
 RetroviridaeHIVTatPseudosubstrate/direct interaction[9]
TAR RNADecoy dsRNA[10]
 FlaviviridaeHepatitis C virusNS5aBlocking of dimerisation/direct interaction[32]
E2Pseudosubstrate/direct interaction[33]
 ReoviridaeReovirusesσ3/σ4dsRNA sequestration[34]
dsRNA
 HerpesviridaeHuman cytomegaloviruspTRS1/pIRS1Interaction and relocalisation/dsRNA sequestration[35]
dsDNA
 HerpesviridaeHerpes simplex virusγ134.5Dephosphorylation of eIF2α substrate[24, 36, 37]
US11dsRNA sequestration/direct interaction
US3/UL13Inhibition of activation
Kaposi's sarcoma herpes virusvIRF2Direct interaction and inhibition of phosphorylation[38]
vIRF3 (LANA2)Inhibition of PKR-induced apoptosis[39]
Epstein–Barr virusEBER RNAsDecoy dsRNA[40]
SMdsRNA sequestration/direct interaction[41]
 PoxiviridaeVaccinia virusE3L (p25/p20)dsRNA sequestration/direct interaction[42, 43]
K3LPseudosubstrate/direct interaction[44]
 AdenoviridaeAdenovirusVAI RNADecoy dsRNA/pseudoactivator[40]

Summary of viral-encoded proteins that mediate evasion of PKR-mediated innate immune response. Viruses are classified by family and type of genome. MERS-CoV: Middle East respiratory syndrome-coronavirus; ss: single-stranded; ds: double-stranded; NSp: nonstructural protein; VP: viral protein; TAR: transactivation responsive; vIRF3: viral IRF3-like protein; EBER: Epstein–Barr virus encoded RNAs; VAI: adenovirus-associated RNA-I; eIF: eukaryotic initiation factor.