PKR Binds Enterovirus IRESs, Displaces Host Translation Factors, and Impairs Viral Translation to Enable Innate Antiviral Signaling

Abstract

Among the RIG-I-like pattern recognition receptors, MDA5 stands out because it senses long dsRNA duplexes independent of their 5′ features (RIG-I recognizes viral [v]RNA 5′-ppp blunt ends).

Early Emergence of 5′ Terminally Deleted Coxsackievirus-B3 RNA Forms Is Associated with Acute and Persistent Infections in Mouse Target Tissues

“…The innate immune response mediated by type 1 IFN is a key step in the progression of acute viral infection, which may evolve toward either healing or chronic infection [39]. The importance of this system is evidenced by the variety of mechanisms used by RNA (+) viruses to evade or inhibit IFN induction, signaling, or effector functions and by the various deleterious phenotypes found in humans and mice with genetic disruptions in IFN-β production or signaling [40,41]. Interestingly, 5 UTR deletions have been reported in hepatitis C virus, dengue virus, foot-and-mouth disease, or African swine fever virus, either during persistent infection or with a reduced virulence with a weak IFN response [25,27,42,43].…”

Move and countermove: the integrated stress response in picorna- and coronavirus-infected cells

“…3C pro has been suggested to play a role in conferring eIF2-independence by removing the N-terminal regulatory domain of eIF5B, which is the eukaryotic homologue of archeal and prokaryotic eIF2, thereby possibly serving a role as noncanonical carrier of Met-tRNA i [28] . Additionally, 3C pro cleaves PKR 29 , 30 , but it is unknown whether this activity is important for suppressing the ISR or, alternatively, for countering a direct antiviral activity of PKR, which was recently shown to inhibit viral translation and activate innate antiviral signaling by binding to the IRES [31] . 3C pro also cleaves G3BP1 [32] , a SG nucleation factor, but it is unclear whether this contributes to SG disruption or serves to counter the recently discovered direct antiviral function of G3BP1 to bind to the viral genome and inhibit viral RNA replication [33] .…”