Abstract
RIG-I triggers antiviral responses by recognizing viral RNA (vRNA) in the cytoplasm. However, the spatio-temporal dynamics of vRNA sensing and signal transduction remain elusive. We investigated the time course of events in cells infected with Newcastle disease virus (NDV), a non-segmented negative-strand RNA virus. RIG-I was recruited to viral replication complexes (vRC) and triggered minimal primary type I interferon (IFN) production. RIG-I subsequently localized to antiviral stress granules (avSG) induced after vRC formation. The inhibition of avSG attenuated secondary IFN production, suggesting avSG as a platform for efficient vRNA detection. avSG selectively captured positive-strand vRNA, and poly(A)+ RNA induced IFN production. Further investigations suggested that uncapped vRNA derived from read-through transcription was sensed by RIG-I in avSG. These results highlight how viral infections stimulate host stress responses, thereby selectively recruiting uncapped vRNA to avSG, in which RIG-I and other components cooperate in an efficient antiviral program.
Highlights
Retinoic acid-inducible gene I (RIG-I), a DExD/H-box RNA helicase family protein, is a crucial cytosolic viral RNA sensor that initiates signal transduction to produce antiviral cytokines, namely, type I and III interferons (IFN-α/β and IFN-λ) [1,2,3,4]
By monitoring the time-course events in Newcastle disease virus (NDV)-infected cells, we demonstrated that RIG-I senses viral RNA (vRNA) that accumulate in viral replication complexes (vRC) and subsequently in host antiviral stress granules (avSG)
We discovered that avSG contains vRNA derived from read-through transcription, which acts as a PLOS Pathogens | DOI:10.1371/journal.ppat
Summary
Retinoic acid-inducible gene I (RIG-I), a DExD/H-box RNA helicase family protein, is a crucial cytosolic viral RNA (vRNA) sensor that initiates signal transduction to produce antiviral cytokines, namely, type I and III interferons (IFN-α/β and IFN-λ) [1,2,3,4]. The RIG-I/IPS-1 interaction leads to the recruitment of a variety of signaling adaptors in order to activate transcription factors including IFN regulatory factors (IRF) 3 and 7 as well as NF-κB. These transcription factors activate the genes coding for cytokines and IFNs in addition to IFNstimulated genes (ISG). A variety of viruses have been shown to induce the formation of SG in infected cells [18], which is strictly regulated in a steady state; once cells are exposed to viral infections, double-stranded RNA (dsRNA)-inducible protein kinase R (PKR) is activated by viral dsRNA (vdsRNA), an intermediate product generated within the viral replicative life cycle [19]. Activated PKR further phosphorylates the eIF2 α-subunit (eIF2α) and recruits SG components to form the complex [13]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
