We found that intracellular poly(I·C) transfection to mimic viral infection enhances the RIG-I/MDA5 (melanoma differentiation-associated gene 5)-mediated dimerization of interferon regulatory factor 3 (IRF-3).
Upon virus infection, LRRC59 specifically interacted with ISG15-associated DDX58 and blocked its association with LRRC25, the secondary receptor to deliver DDX58 to autophagosomes for SQSTM1/p62-dependent degradation, leading to the stronger antiviral immune responses.
TRAF3 appears to undergo sequential ubiquitin "immuno-editing" following virus infection that is crucial for regulation of RIG-I-dependent signaling to the antiviral response.
This is critical for promoting the growth and survival of T lymphocytes as well as the regulation of the RIG-I helicase pathway for type I interferon production in response to viral infections.
These results suggest that PACT plays an important role in potentiating RIG-I function to produce type I IFNs in order to restrict arenavirus replication and that viral NP RNase activity is essential for optimal viral replication by suppressing PACT-induced RIG-I activation.<b>IMPORTANCE</b> We report here a new role of the nucleoproteins of arenaviruses that can block type I IFN production via their specific inhibition of the cellular protein sensors of virus infection (RIG-I and PACT).
The use of a human cell line expressing a debilitated RIG-I molecule, together with overexpression studies of wild type RIG-I, showed that the IFN-beta induction by virus infection or by leader RNA required RIG-I to be functional.
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 patter (PAMP) motifs within RNA ligands that accumulate during virus infection.
Sumoylation of the caspase recruitment domains of MDA5 and RIG-I is also required for their dephosphorylation by PP1 and activation upon viral infection.
Specifically, we demonstrate that DRH-1/RIG-I is required for inducing the IPR in response to Orsay virus infection, but not in response to other triggers like microsporidian infection or proteotoxic stress.
Resolving influenza infection in mammals has been shown to require RIG-I; however, the apparent absence of a RIG-I homolog in chickens raises intriguing questions regarding how this species deals with influenza virus infection.
Neuronal transcriptomic responses to Japanese encephalitis virus infection with a special focus on chemokine CXCL11 and pattern recognition receptors RIG-1 and MDA5.
Mechanistically, Lnczc3h7a binds to both TRIM25 and activated RIG-I, serving as a molecular scaffold for stabilization of the RIG-I-TRIM25 complex at the early stage of viral infection.
IRF-3 depletion was dependent on a productive HIV-1 replication cycle and caused the specific disruption of Toll-like receptor and RIG-I-like receptor innate immune signaling that rendered cells permissive to secondary virus infection.
Compared with H1N1 virus-induced mediators, H5N1 mediators markedly enhance the cytokine response to PolyIC and to both seasonal and H5N1 virus infection in a RIG-I-dependent manner.
Apart from TLRs, other PRRs such as RIG-1 and MDA-5 are also able to recognize viral infection and participate in the activation of type I interferon synthesis.
A recent study found that the delivery of circRNAs generated <i>in vitro</i> activates RIG-I-mediated innate immune responses and provides protection against viral infection.
RIG-I (Retinoic acid-inducible gene I) and MDA5 (Melanoma Differentiation-Associated protein 5), collectively known as the RIG-I-like receptors (RLRs), are key protein sensors of the pathogen-associated molecular patterns (PAMPs) in the form of viral double-stranded RNA (dsRNA) motifs to induce expression of type 1 interferons (IFN1) (IFNα and IFNβ) and other pro-inflammatory cytokines during the early stage of viral infection.