RIG-I goes beyond naked recognition

Abstract

It is currently unclear at which point during viral replication that RNA genomes are first recognized as nonself by the immune system. In this issue of Cell Host & Microbe, Weber et al. show that incoming nucleocapsid-bound genomes are sufficient to bind and activate innate immune sensors.

Figure 1.. Nature and Availability of RIG-I Ligands during the Virus Replication Cycle

Encapsidated viral RNA with 5′ PPP groups and proper secondary structures for RIG-I recognition are relatively few in number shortly after virus entry. The coated viral RNA (vRNA) interacts with the C-terminal domain of RIG-I to allow activation of RIG-I and association with IPS-1 present on peroxisomes to initiate ISGs mediated early antiviral response. vRNA is replicated and transcribed in the nucleus (in the case of influenza A virus, illustrated here) or in the cytoplasm (many other RNA viruses) to produce abundant messenger RNA (mRNA) (coated or capped?) and vRNA with 5′ PPP (coated?) available for optimal RIG-I activation and IFN production via IPS interaction present on mitochondria. Although RIG-I can be activated by either naked or encapsidated viral RNA, whether the different ligands induce similar or different structural rearrangements (“X” or “Y” conformation) is not clear.