The Thermodynamic Basis for Viral RNA Detection by the RIG-I Innate Immune Sensor

Abstract

Background: RIG-I is an essential innate immune receptor that detects viral RNAs in infected cells.Results: RIG-I uses distinct subdomains to recognize specific characteristics of viral RNAs.Conclusion: The 5′-triphosphate is critical for high affinity RIG-I/RNA interaction.Significance: Characterizing the RIG-I/RNA interface is essential for understanding early stages of immune response against RNA viruses.

A structure-based model of RIG-I activation

“…This is because, for internal binding, only the helicase can be involved; the CTD, for steric reasons, cannot bind. Evidence for this is the significantly lower affinity of the helicase domain alone for dsRNA compared to full-length RIG-I Vela et al 2012), and that 2:1 complexes of RIG-I on 60-mer dsRNA have been detected, most likely with one RIG-I capping each end (Kowalinski et al 2011). Nevertheless, internal binding may be sufficient to displace the CARDS and also allow translocation of RIG-I along dsRNA.…”

Parts, assembly and operation of the RIG-I family of motors

“…Short RNA duplexes are readily recognized by RIG-I, but the highest affinity ligands are RNA duplexes containing a 5′-triphosphate [41,42], which are typical products of viral RNA replication. The strongest interactions within the entire complex are observed between the CTD and the triphosphosphorylated duplex terminus [43].…”

Toward a crystal-clear view of the viral RNA sensing and response by RIG-I-like receptors

“…This design allows RIG-I to examine the correct chemistry and structure of the RNA ligand. [30][31][32][33] …”