Moreover, tiny LNA inhibition of miR-17-5p, miR-142-3p, and BART10-3p upregulated endogenous BHRF1 protein in Jijoye cells (Figure 4E), especially when used in combination (Figure 4E, lane 5). Together, these results confirm that EBV and host miRNAs co-repress the BHRF1 mRNA, reducing protein output, and that host and viral miRNAs can have a cumulative effect on targets.
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.
In addition to miR-BART10, we observed significant inhibition of the EBV BHRF1 3'UTR reporter in the presence of miR-BART1. miR-BART1-3p and its rLCV homolog, miR-rL1-6-3p, have seed matches (nt 2 to 8) to the EBV and rLCV BHRF1 3'UTRs, although the positions of the seed match sites and the miRNA inhibition are not conserved.
