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.
Plasmacytoid dendritic cells (pDCs) are a specialized subset of DCs capable of rapidly producing copious amounts of type I IFN (IFN-I) in response to viral infections.
Conversely, the loss of IFN-I responsiveness increases susceptibility to viral infections, but, surprisingly, most affected individuals survive despite these inborn errors of immunity.
As in mammals, expression of different salmon IFN-I in response to virus infection is dependent on their promoters, properties of the virus and the cell's expression of nucleic acid receptors and interferon regulatory factors (IRFs).
We demonstrated here that YY1 interacts with STAT1 and dynamically regulates the induction of IFN-1 production and activation of IFN-1 signaling in different stages during viral infection.
IFN regulatory factor 3 (IRF3) is the master transcription factor that controls IFN-I production via phosphorylation-dependent dimerization in most cell types in response to viral infections and various innate stimuli by pathogen-associated molecular patterns (PAMPs).
Plasmacytoid dendritic cells (pDCs) are the major type I interferon (IFN-I)-producing cells, and IFN-I actually contributes to pathogenesis during chronic viral infections.
The fatal outcome of virus infection as well as the efficiency of IFN-I-based antiviral therapies in its prevention, are determined by complex interactions between viral virulence factors and cellular antiviral IFN-I inducible factors.