Epstein-Barr Virus Early Protein BFRF1 Suppresses IFN-β Activity by Inhibiting the Activation of IRF3

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.

The Expression of ephrinA1/ephA2 Receptor Increases in Chronic Rhinosinusitis and ephrinA1/ephA2 Signaling Affects Rhinovirus-Induced Innate Immunity in Human Sinonasal Epithelial Cells

“…Epidermal ephA2 expression is upregulated in keratinocytes by several pro-inflammatory cytokines, growth factors, and ultraviolet radiation ( 45 ). Hypoxia upregulates both molecules in the skin and lung ( 29 , 46 ). In endothelial cells, proinflammatory cytokines including TNF-α and IL-1β induced the expression of ephrinA1/ephA2 ( 47 ).…”

“…Knockdown of ephA2 significantly reduced KSHV entry and EphA2 overexpression significantly increased EBV infection ( 26 – 28 ). An EBV-encoded early lytic protein, BERF1, inhibited the IFN-β production, disrupting the host innate immunity ( 29 ).…”

The Complex Regulatory Role of Cytomegalovirus Nuclear Egress Protein pUL50 in the Production of Infectious Virus

“…HCMV pUL50 and pUL53, like their respective herpesviral homologs, are the core NEC components and major egress regulators. Although the main functions, structural features, and binding properties of these core NEC proteins have been well recognized, several accessory activities have been reported, in particular for the pUL50 groove protein homologs [50][51][52][53][54][55]. In the present study, we focused on directly NEC-dependent and partly NEC-independent functional aspects of HCMV pUL50 through the characterization of the HCMV ∆UL50 deletion mutant.…”

A STING inhibitor suppresses EBV‐induced B cell transformation and lymphomagenesis

“…We also identified STING The regulatory mechanisms by which EBV escapes the innate immune response triggered by primary infection, and the reactivation molecules, have been well characterized. 22,43 KSHV-ORF52 and EBV BLRF2 homologs directly interact with cGAS to control its enzymatic activity. 44 More recently, it was found that EBV BGLF2 binds to STING and suppresses type I IFN production.…”