Abstract
Epstein-Barr virus (EBV) is the causative agent of infectious mononucleosis that is closely associated with several human malignant diseases, while type I interferon (IFN-I) plays an important role against EBV infection. As we all know, EBV can encode some proteins to inhibit the production of IFN-I, but it’s not clear whether other proteins also take part in this progress. EBV early lytic protein BFRF1 is shown to be involved in viral maturation, however, whether BFRF1 participates in the host innate immune response is still not well known. In this study, we found BFRF1 could down-regulate sendai virus-induced IFN-β promoter activity and mRNA expression of IFN-β and ISG54 during BFRF1 plasmid transfection and EBV lytic infection, but BFRF1 could not affect the promoter activity of NF-κB or IRF7. Specifically, BFRF1 could co-localize and interact with IKKi. Although BFRF1 did not interfere the interaction between IKKi and IRF3, it could block the kinase activity of IKKi, which finally inhibited the phosphorylation, dimerization, and nuclear translocation of IRF3. Taken together, BFRF1 may play a critical role in disrupting the host innate immunity by suppressing IFN-β activity during EBV lytic cycle.
Highlights
Innate immunity is the first line of host conservative and rapid defense against pathogen invasion, of which type I interferon (IFN-I) plays an important role in the antiviral immune response [1]
The activity of IFN-b promoter was obviously induced by Sendai virus (SeV), which was significantly inhibited by the ectopic expression of BFRF1 (Figure 1A), with similar inhibitory effect to the positive control BGLF4 [14]
Expression plasmid BFRF1Flag, BGLF4-HA, or vector was transfected into HEK293T cells to see whether BFRF1 can regulate the mRNA expression of IFN-b and its downstream gene, such as ISG54
Summary
Innate immunity is the first line of host conservative and rapid defense against pathogen invasion, of which type I interferon (IFN-I) plays an important role in the antiviral immune response [1]. RNA helicases retinoic acid inducible gene 1 (RIG-I) and melanoma differentiation-associated gene 5 (MDA-5) are the most vital RLRs and are reported to exert essential roles in the detection of intracellular dsRNA, which signal through IFN promoter stimulator 1 (IPS-1) to activate the kinases TANK-binding kinase 1 (TBK1) and inducible. It’s shown that many EBV-encoded gene products are involved in the innate immunity, and some of which can stimulate the production of IFN-I. EBV-encoded small nuclear RNA 1 (EBER1) and EBER2 act as ligand of RIG-I to activate IRF3 [10, 11]. Some EBV-encoded gene products are demonstrated to inhibit the production of IFN-b. EBV-encoded RNA miR-BART6-3p inhibits EBV-triggered IFN-b response and facilitates EBV infection through targeting the 3′UTR of RIG-I mRNA [18]
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