The many ways Epstein-Barr virus takes advantage of the RNA tool kit

Abstract

ABSTRACT Epstein-Barr virus (EBV) was the first human cancer-causing virus to be discovered over fifty years ago. Given its relatively large genome size for a virus and hence the capacity to store more than mere protein-coding information, EBV also harbours genetic material for producing an array of distinct noncoding (nc)RNAs. The double-stranded nature of its DNA genome allows the utilization of the whole gamut of ncRNA types, including both RNA polymerase II and III transcripts, in devising a sophisticated strategy to ensure its replication upon infection in host cells and evasion of host immune responses. Owing to the development of sensitive technologies in recent years, mostly entailing next-generation sequencing, the list of ncRNA types generated by EBV has expanded now to include two RNAs (EBER1 and EBER2) best categorized as long ncRNAs, dozens of microRNAs, one small nucleolar RNA, stable intronic sequence RNAs, and the most recently discovered circular RNAs. With the application of cutting-edge technology, the molecular mechanisms of some of these noncoding transcripts are beginning to emerge, while others remain yet to be elucidated. As viruses often take advantage of existing molecular pathways established by the host, it is likely that further novel concepts of the greatly unexplored noncoding world can be learned from studying the many EBV ncRNAs.