Elsevier

Current Opinion in Virology

Volume 1, Issue 3, September 2011, Pages 167-176
Current Opinion in Virology

RIG-I like receptors and their signaling crosstalk in the regulation of antiviral immunity

https://doi.org/10.1016/j.coviro.2011.04.004Get rights and content

During virus infection, multiple immune signaling pathways are triggered, both within the host cell and bystander cells of an infected tissue. These pathways act in concert to mediate innate antiviral immunity and to initiate the inflammatory response against infection. The RIG-I-like receptor (RLR) family of pattern recognition receptors (PRRs) is a group of cytosolic RNA helicase proteins that can identify viral RNA as nonself via binding to pathogen associated molecular pattern (PAMP) motifs within RNA ligands that accumulate during virus infection. This interaction then leads to triggering of an innate antiviral response within the infected cells through RLR induction of downstream effector molecules such as type I interferon (IFN) and other pro-inflammatory cytokines that serve to induce antiviral and inflammatory gene expression within the local tissue. Cellular regulation of RLR signaling is a critical process that can direct the outcome of infection and is essential for governance of the overall immune response and avoidance of immune toxicity. Mechanisms of positive and negative regulation of RLR signaling have been identified that include signaling crosstalk between RLR pathways and nuclear oligomerization domain (NOD)-like receptor (NLR) pathways and Caspase networks. Furthermore, many viruses have evolved mechanisms to target these pathways to promote enhanced replication and spread within the host. These virus–host interactions therefore carry important consequences for host immunity and viral pathogenesis. Understanding the pivotal role of RLRs in immune regulation and signaling crosstalk in antiviral immunity may provide new insights into therapeutic strategies for the control of virus infection and immunity.

Highlights

► Distinct subsets of ssRNA, dsRNA and dsDNA viruses trigger RIG-I and MDA5 activation of IPS-1. ► RLR signaling is regulated through multiple protein modifications by host cellular factors. ► Viral proteins antagonize multiple components of the RLR signaling pathway to subvert immunity. ► RLR, NLR and Caspase crosstalk promote alternate recognition pathways to sense cytosolic infection.

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