Neuronal transcriptomic responses to Japanese encephalitis virus infection with a special focus on chemokine CXCL11 and pattern recognition receptors RIG-1 and MDA5.
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.
Viral infection caused translocation of hnRNPM from the nucleus to the cytoplasm. hnRNPM interacted with RIG-I and MDA5, and impaired the binding of the RLRs to viral RNA, leading to inhibition of innate antiviral response.
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).
Retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs), including RIG-I, melanoma-differentiation-associated gene 5 (MDA5), and LGP2, function as cytoplasmic virus sensor proteins during viral infection.
In conclusion, pOASL suppresses CSFV replication via the MDA5-mediated type I IFN-signaling pathway.<b>IMPORTANCE</b> The host innate immune response plays an important role in mounting the initial resistance to viral infection.
For example, the protein encoded by the IFIH1 gene is associated with the function of viral infection in the immune system, which affects the survival rate of large yellow croakers.
Sumoylation of the caspase recruitment domains of MDA5 and RIG-I is also required for their dephosphorylation by PP1 and activation upon viral infection.
Knockdown or knockout of endogenous RNF123 potentiates IFN-β production triggered by SeV and EMCV, but not by the sensor of DNA viruses cGAS RNF123 associates with RIG-I and MDA5 in both endogenous and exogenous cases in a viral infection-inducible manner.
RIG-I-like receptors (RLRs: RIG-I, MDA5 and LGP2) play a major role in the innate immune response against viral infections and detect patterns on viral RNA molecules that are typically absent from host RNA.
The IFIH1 gene encodes a cytoplasmic receptor of the pattern-recognition receptors (PRRs) family that recognizes dsRNA, playing a role in the innate immune response triggered by viral infection.
Virus infection can initiate a type I interferon (IFN-α/β) response via activation of the cytosolic RNA sensors retinoic acid-inducible gene-I (RIG-I) and melanoma differentiation-associated gene 5 (MDA5).
IFIH1 affects several immune-related diseases, including psoriasis and chronic periodontitis, and provides a molecular link between genetic susceptibility, viral infections and immune-related diseases.
Two RNA helicases, retinoic acid inducible gene-I (RIG-I) and melanoma differentiation-associated gene 5 (MDA5), are recently identified as cytoplasmic PPRs for virus infection.
Our findings suggest that variants in IFIH1 confer different susceptibility to diverse viral infections and provide insight into the relationship between adaptation to past infection and predisposition to autoimmunity in modern populations.
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.
Given that RNA helicase encoded by MDA-5 is a critical molecule involved in the innate immune defense against viruses, viral infection may play an important role in the pathogenesis of C-ADM and rapidly progressive ILD.