The protein kinase regulated by RNA, PKR, plays an important function in innate immune response. The N-terminal includes a repeated domain that confers dsRNA-binding activity while the C-terminal confers the kinase activity. The best characterized substrate of PKR is the alpha-subunit of protein synthesis initiator 2 (eIF-2alpha). When phosphorylated by PKR, eIF-2alpha leads to an inhibition of translation. Therefore, PKR is a key factor in the host antiviral response, through inhibition of protein synthesis during viral infection.
Viruses have evolved specific mechanisms to prevent the establishment of an antiviral state by inhibiting key components of the signaling pathway . For instance, several viral proteins antagonists of PKR have been identified, many of which are RNA-binding proteins. Among them, E3L and K3L from vaccinia and sigma3 protein from reoviruses. E3L was found to inhibit host PKR activity through direct interaction. Hepatitis C virus NS5A, Herpes simplex 1 US11, and Kaposi's sarcoma vIRF-2 protein also interact with and inhibit PKR. Some viruses including HCMV or MCMV alter PKR subcellular localization while others direct PKR to degradation like Rift valley fever virus NSs protein.