Innate Immune Detection of Cardioviruses and Viral Disruption of Interferon Signaling

Abstract

Cardioviruses are members of the Picornaviridae family and infect a variety of mammals, from mice to humans. Replication of cardioviruses produces double stranded RNA that is detected by helicases in the RIG-I-like receptor family and leads to a signaling cascade to produce type I interferon. Like other viruses within Picornaviridae, however, cardioviruses have evolved several mechanisms to inhibit interferon production. In this review, we summarize recent findings that have uncovered several proteins enabling efficient detection of cardiovirus dsRNA and discuss which cell types may be most important for interferon production in vivo. Additionally, we describe how cardiovirus proteins L, 3C and L∗ disrupt interferon production and antagonize the antiviral activity of interferon effector molecules.

PKR activity modulation by phosphomimetic mutations of serine residues located three aminoacids upstream of double-stranded RNA binding motifs

“…8 a). These steps can further be modulated by interaction of PKR with proteins such as PACT 17 , TRBP 21 and p58IPK 20 by RNA–protein interactions involving helicases 37 , and by post-translational modifications such as SUMOylation 38 . More recently, PKR was reported to be regulated through binding of a non-coding RNA nc886, which can act either as a strong PKR repressor or as a weak positive regulator, according to its conformation 39 , 40 .…”

Varicella-Zoster Virus ORF9 Is an Antagonist of the DNA Sensor cGAS

“…We used these Z-scores to rank ORFs in their ability to block IFN activation downstream of cGAS/STING (Figure 2A). KSHV ORF52, a previously described cGAS-antagonist (Wu et al, 2015), and the L protein of EMCV, a previously described IRF3-antagonist (Freundt et al, 2018), served as positive controls. As expected, we found these with the lowest ranks (i.e.…”

Nucleocytoplasmic Trafficking Perturbation Induced by Picornaviruses

“…The first implication of another viral protein in nucleocytoplasmic trafficking perturbation was reported by Delhaye et al, who showed that TMEV-induced mislocalization of the nuclear protein PTB depended on the leader (L) protein [ 31 ]. L proteins of cardioviruses are very small proteins of 67–76 amino acids lacking any enzymatic activity [ 58 , 59 ]. Using transfection of EMCV replicons lacking either 2A or L and introduction of in vitro-translated proteins into digitonin-permeabilized cells, Lidsky et al confirmed that L but not 2A was required for nucleocytoplasmic traffic perturbation [ 43 ].…”