Double-stranded RNA-dependent protein kinase (PKR) in antiviral defence in fish and mammals

Abstract

The interferon-inducible double-stranded RNA-dependent protein kinase (PKR) is one of the key antiviral arms of the innate immune system. Upon binding of viral double stranded RNA, a viral Pattern Associated Molecular Pattern (PAMP), PKR gets activated and phosphorylates the eukaryotic translation initiation factor 2α (eIF2α) resulting in a protein shut-down that limits viral replication. Since its discovery in the mid-seventies, PKR has been shown to be involved in multiple important cellular processes including apoptosis, proinflammatory and innate immune responses. Viral subversion mechanisms of PKR underline its importance in the antiviral response of the host. PKR activation pathways and its mechanisms of action were previously identified and characterised mostly in mammalian models. However, fish Pkr and fish-specific paralogue Z-DNA-dependent protein kinase (Pkz) also play key role in antiviral defence. This review gives an update on the current knowledge on fish Pkr/Pkz, their conditions of activation and their implication in the immune responses to viruses, in comparison to their mammalian counterparts.