摘要：

UNLABELLED: (EBV) is a associated with various . Rather than going through the lytic cycle, EBV maintains latency by limiting the expression of viral genes in . Viral microRNAs (miRNAs) of some herpesviruses have been reported to directly target immediate early genes and suppress lytic induction. In this study, we investigated whether BamHI-A rightward transcript () miRNAs targeted two EBV immediate early genes, and . Bioinformatic analysis predicted that 12 different miRNAs would target . Of these, the results of a reporter assay indicated that only one interacted with the 3' untranslated region (UTR) of : miR-BART20-5p. miR-BART20-5p's effect on gene expression involved two putative seed match sites in the 3' UTR, but a mutant version of the miRNA, miR-BART20-5pm, had no effect on expression. As expected from the fact that the entire 3' UTR of resides within the 3' UTR of , miR-BART20-5p interacted with the 3' UTR of as well. and and protein expression was suppressed in cells of an cell line infected with the recombinant Akata strain of EBV (-EBV) transfected with a miR-BART20-5p mimic. The expression of various EBV early proteins was also suppressed by the miR-BART20-5p mimic. In contrast, and expression in -EBV cells transfected with a miR-BART20-5p inhibitor was enhanced. Furthermore, progeny virus production was suppressed by the miR-BART20-5p mimic and enhanced by the miR-BART20-5p inhibitor in -EBV cells induced for the lytic cycle. Our data suggest that miR-BART20-5p plays a key role in latency maintenance in EBV-associated by directly targeting immediate early genes.: Herpesviruses maintain latency using various mechanisms and establish lifelong in the . From time to time, herpesviruses are reactivated and express immediate early genes which trigger a lytic cascade, leading to the production of progeny . Recently, some herpesviruses have been shown to use their own microRNAs (miRNAs) to downregulate immediate early genes to inhibit the lytic cycle. This study presents evidence that EBV also downregulates two immediate early genes by miR-BART20-5p to suppress the lytic cycle and progeny virus production. Overall, this is the first study to report the direct regulation of EBV immediate early genes by an EBV miRNA, implying its likely importance in latency maintenance in EBV-associated .

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