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Epstein-Barr virus miR-BHRF1-2 targets retinoic acid-inducible gene I and inhibits interferon release in primary B cells
Epstein-Barr virus (EBV) was discovered in 1964 and was the first identified human tumor-associated virus. EBV has been found to cause 2% of malignant tumors worldwide and it is etiologically associated with various malignancies such as Burkitt’s lymphoma, Hodgkin’s lymphoma, nasopharyngeal carcinoma. MicroRNAs (miRNAs) are small noncoding RNAs of 19-22 nt in length that post-transcriptionally regulate gene expression. EBV is the first human virus that has been reported to encode miRNAs, including 4 mature BHRF1 miRNAs and 40 mature BART miRNAs. EBV miRNAs can be expressed in all phases of its complicated life cycle and are potentially involved in the regulation of hundreds of genes. However, their characteristics are just beginning to emerge. In my project, I found that EBV miRNAs were involved in the inhibition of innate immune responses. Among all 44 miRNAs, EBV-encoded miR-BHRF1-2 was identified as a novel viral immune-evasion factor that inhibited IFN-α release. EBV miR-BHRF1-2 targeted RIG-I, a viral double-stranded RNA (dsRNA) sensor that mediates IFN-α production, inducing the downregulation of RIG-I protein expression in EBV-infected B cells. My results further demonstrate the important role of miR-BHRF1-2 in the antiviral immune evasion and establishment of EBV infection, which may provide new targets for the treatment of EBV-associated malignancies.
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