The mitochondrial transcription factor A (TFAM), plays a vital role in mitochondrial DNA (mtDNA) metabolism and has been suggested to influence IFN-β production in response to viral infection.
Here, we found that H3K79me2/3 modification levels at the Il6 and Ifnb1 promoters, as well as H3K79me2 modification at the Tnfα promoter, were increased in macrophages activated by Toll-like receptor (TLR) ligands or virus infection.
However, the functional role of early interferon β (IFNβ) and its cellular source during sepsis in the context of preexisting viral infections has not been defined.
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.
Our study revealed that demethylating CpGs downstream of the IFN-β transcription start site using a CRISPR/dCas9 system suppressed viral replication during subsequent influenza virus infection.
Understandably, an increased IFN-β level facilitated phosphorylation of STAT1 to induce expression of innate antiviral genes Mx1 and ISG15, suggesting that TLR4 overexpressing macrophages were equipped better against viral infection.
After stimulation with polyinosinic-polycytidylic acid (poly I:C) (0.25 μg/ml) for 4 h to mimic viral infection, 293FT wild-type (WT) and IRF7-Δ7 cells were treated with 0, 1, or 100 μM nicotine for 24 h, which increased IFN-β expression in both types of cells but elevation was higher in WT cells (p < 0.001).
Type I interferons (IFNs) (IFN-α, IFN-β) and type III IFNs (IFN-λ) share many properties, including induction by viral infection, activation of shared signaling pathways, and transcriptional programs.
We show that viruses lacking nsp14 ExoN activity are more sensitive than wild-type MHV to restriction by exogenous IFN-β and that viruses produced in the presence of an antiviral state are less capable of establishing a subsequent viral infection.
Here, we identified metabolite-sensing GPCR TGR5 as an interferon (IFN)-stimulated gene (ISG) which had increased expression following viral infection or IFN-β stimulation in a STAT1-dependent manner.
The haplotype variant AGCA, which is mainly present in Hebao pigs, significantly synergized the poly(I:C)-induced activation of transcription factors, including NF-κB and IFN-stimulated response element (ISRE)-binding factors, and the expression of interferon β, indicating that the variant contributes to the induction or magnitude of the immune response upon viral infection.
Interestingly, rSmp76 did not inactivate the viral particles directly but suppressed the establishedviral infection, similar to the effect of interferon (IFN)-β. Mechanistically, rSmp76 was revealed to upregulate the expression of IFN-β by activating interferon regulatory transcription factor 3 (IRF3) phosphorylation, enhancing the type-I IFN response and inhibiting viral infection.
Therefore, this newly revealed mechanism shows that cellular response leads to transfer of AGO2 from cell nucleus and promotes IFN-β expression to increase host survival during viral infection.
The role of IFN-β in protection against viral infections is well established and has been studied for decades, but its role in mycobacterial infections remains much more complicated and debatable.
Innate immunity is the first line of defense against virus infections and is marked by production of type I interferons (IFN), a family of cytokines that includes IFN-β and several IFN-αs.
Furthermore, we found that ML323, a specific USP1-UAF1 inhibitor, attenuated IFN-β expression and enhanced viral replication both in vitro and in vivo<i>.</i> Therefore, our results outline a novel mechanism for the control of TBK1 activity and suggest USP1-UAF1 complex as a potential target for the prevention of viral diseases.