Abstract

MicroRNAs (miRNAs) are small RNAs that play important roles in the regulation of gene expression. First described as posttranscriptional gene regulators in eukaryotic hosts, virus-encoded miRNAs were later uncovered. It is now apparent that diverse virus families, most with DNA genomes, but at least some with RNA genomes, encode miRNAs. While deciphering the functions of viral miRNAs has lagged behind their discovery, recent functional studies are bringing into focus these roles. Some of the best characterized viral miRNA functions include subtle roles in prolonging the longevity of infected cells, evading the immune response, and regulating the switch to lytic infection. Notably, all of these functions are particularly important during persistent infections. Furthermore, an emerging view of viral miRNAs suggests two distinct groups exist. In the first group, viral miRNAs mimic host miRNAs and take advantage of conserved networks of host miRNA target sites. In the larger second group, viral miRNAs do not share common target sites conserved for host miRNAs, and it remains unclear what fraction of these targeted transcripts are beneficial to the virus. Recent insights from multiple virus families have revealed new ways of interacting with the host miRNA machinery including noncanonical miRNA biogenesis and new mechanisms of posttranscriptional cis gene regulation. Exciting challenges await the field, including determining the most relevant miRNA targets and parlaying our current understanding of viral miRNAs into new therapeutic strategies. To accomplish these goals and to better grasp miRNA function, new in vivo models that recapitulate persistent infections associated with viral pathogens are required.

Highlights

  • In recent years, non-protein-coding regulatory RNAs have been the subject of increasing interest in both prokaryotic and eukaryotic fields

  • It is likely that new functions and classes remain to be described, diverse noncoding RNA (ncRNA) have already been implicated in regulating gene expression at multiple levels, including chromatin modification, transcription, and posttranscriptional mechanisms

  • RNA interference (RNAi), the process whereby small ncRNAs (,30 nts) serve to direct gene silencing via specific protein machinery, is evolutionarily conserved throughout most eukaryotes

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Summary

Introduction

Non-protein-coding regulatory RNAs have been the subject of increasing interest in both prokaryotic and eukaryotic fields. At least once and possibly multiple times, eukaryotic lineages have evolved to use components of the RNAi machinery to regulate self protein-coding gene expression via a class of small RNAs called microRNAs (miRNAs) [18]. Given the often subtle nature of miRNA-mediated regulation, it is likely that most virus-encoded miRNAs may have a diminished role during lytic infection where robust changes in host and viral gene expression dominate even though viral miRNAs are typically detectable at these times. Natural viruses that encode miRNAs have a DNA component to their replication cycle, replicate in the nucleus where they have full access to the initiating host miRNA biogenesis machinery, and undergo longterm persistent infections These include viruses with DNA genomes (The Herpesvirus, Polyomavirus, Ascovirus, Baculovirus, Iridovirus, and Adenovirus families) and at least one member of the retrovirus family, bovine leukemia virus (BLV) (Table 1). There is a lack of accessible animal models for some viruses that encode miRNAs, and most viral miRNAs encoded by human viruses are not conserved in

Bombyx mori nucleopolyhedrosis virus
Prolonging Longevity of Infected Cells
Findings
The Future
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