Genetics of Epstein-Barr virus microRNAs

The Epstein-Barr virus encodes at least 44 microRNAs that are grouped in two clusters located around the BHRF1 gene and within the BART transcript. The expression pattern of these microRNAs both depends on the lineage of the infected cells and on the type of viral latency. Whilst BART microRNAs are expressed in all EBV-infected tumors, the BHRF1 locus is nearly exclusively expressed in cells that display a type III latency. However, the BART microRNA expression level is several orders of magnitude higher in epithelial cells than in B cells. Genetic studies have demonstrated that the BHRF1 microRNA cluster enhances the initial phases of primary B cell transformation through inhibition of apoptosis. A similar role has been ascribed to the BART microRNAs although their contribution to this process seems more limited. These microRNAs also enhance the survival of B cell lymphoma cells. Using various strategies including high throughput assays, several groups have identified mRNAs targeted by the EBV microRNAs. Here we compare the results of the published high throughput screens and review the viral and cellular genes thought to represent high confidence targets for the EBV microRNAs. Although genetic studies allow unequivocal evaluation of the functions served by the microRNAs, only a few key targets have been identified so far.