Here, we report that EBV-encoded BART miRNAs target the 3'UTR of the LMP1 gene and negatively regulate LMP1 protein expression. These miRNAs also modulate LMP1-induced NF-kaapaB signaling and alleviate the cisplatin sensitivity of LMP1-expressing NPC cells
From the targets identified to date (Table 1, Figure 1) it is apparent that viral miRNAs play an important role in immune evasion by inhibiting immune surveillance and extending the life of the infected host cell. Table 1 Immunomodulatory viral miRNAs.
In some cases, the target viral mRNA is regulated by multiple miRNAs. Several of the EBV BART miRNAs from a single genomic cluster(BART1-5p, BART3-5p, BART16, and BART17-5p) work together to down-regulate production of the EBV latency membrane protein 1(LMP1).
EBV miR-BART1, -16, and -17 reduce the expression of EBV LMP1 to prevent its overexpression.LMP1 without a ligand drives proliferation of EBV-infected B cells by signaling within the B cells similar to the signaling of the cellular CD40 receptor.
An overview of known targets of cellular or viral targets is given in tables 2 and 3.Table 2 Cellular Targets of viral miRNAs.Table 3 Viral Targets of viral miRNAs.
EBV-encoded BART miRNAs target the 3'-UTRs of viral genes, such as LMP1, BALF5, and LMP2A genes, and negatively regulate expression of these viral genes.On the other hand, EBV miRNAs repress cellular proteins, which include p53 up-regulated modulator of apoptosis(PUMA), DICER1, and BIM. Table 2 EBV-derived miRNAs and their target genes.
