EBV Noncoding RNAs

Abstract

EBV expresses a number of viral noncoding RNAs (ncRNAs) during latent infection, many of which have known regulatory functions and can post-transcriptionally regulate viral and/or cellular gene expression. With recent advances in RNA sequencing technologies, the list of identified EBV ncRNAs continues to grow. EBV-encoded RNAs (EBERs), the BamHI-A rightward transcripts (BARTs), a small nucleolar RNA (snoRNA), and viral microRNAs (miR-NAs) are all expressed during EBV infection in a variety of cell types and tumors. Recently, additional novel EBV ncRNAs have been identified. Viral miRNAs, in particular, have been under extensive investigation since their initial identification over ten years ago. High-throughput studies to capture miRNA targets have revealed a number of miRNA-regulated viral and cellular transcripts that tie into important biological networks. Functions for many EBV ncRNAs are still unknown; however, roles for many EBV miRNAs in latency and in tumorigenesis have begun to emerge. Ongoing mechanistic studies to elucidate the functions of EBV ncRNAs should unravel additional roles for ncRNAs in the viral life cycle. In this chapter, we will discuss our current knowledge of the types of ncRNAs expressed by EBV, their potential roles in viral latency, and their potential involvement in viral pathogenesis.

MicroRNAs of Epstein-Barr Virus Control Innate and Adaptive Antiviral Immunity

“…In this light, it is remarkable to learn that miRNAs of different members of the herpesvirus family are distinct, sharing little sequence conservation, with few exceptions (15,42). Lack of sequence conservation imposes a general difficulty for researchers because conservation across species is one of the best parameters to predict the targets of miRNAs.…”

The Immune Response to Epstein Barr Virus and Implications for Posttransplant Lymphoproliferative Disorder

“…Finally, EBV was the 1st human virus shown to encode miRNA (56), small noncoding RNA that participate in posttranscriptional gene regulation and are integral to a host of cellular processes including proliferation, survival, differentiation, and metabolism (57). We now know that viral miRNA can significantly impact the regulation of these processes in infected cells resulting in altered susceptibility to recognition and elimination by the immune system.…”

Japanese Macaque Rhadinovirus Encodes a Viral MicroRNA Mimic of the miR-17 Family

“…Expressed by all multicellular organisms, miRNAs regulate many important biological processes, including development, homeostasis, hematopoiesis, and the development of immune responses. Aberrant miRNA expression patterns have been linked to disease states and clinical outcomes (12)(13)(14)(15). Pathogen encounters, such as those during virus infection, can perturb the cellular miRNA environment (13,16).…”

“…Pathogen encounters, such as those during virus infection, can perturb the cellular miRNA environment (13,16). A number of viruses, particularly the herpesviruses, encode viral miRNAs that play important roles throughout the viral life cycle and can contribute to pathogenesis through the regulation of expression of both host and viral genes (7,12,13,15).…”

“…Studies on KSHV and EBV indicate that many viral miRNAs contribute to persistent infection and viral latency by attenuating antiviral immune responses and enhancing intrinsic cell signaling pathways that promote the survival and proliferation of infected cells (12,13,15,16). KSHV miR-K10a, for example, targets TWEAKR (tumor necrosis factor [TNF]-like weak inducer of apoptosis receptor), which can protect infected cells from apoptosis and dampen proinflammatory cytokine responses (30).…”