Virus-encoded microRNAs

Abstract

microRNAs (miRNAs) are the subject of enormous interest. They are small non-coding RNAs that play a regulatory role in numerous and diverse cellular processes such as immune function, apoptosis and tumorigenesis. Several virus families have been shown to encode miRNAs, and an appreciation for their roles in the viral infectious cycle continues to grow. Despite the identification of numerous (>225) viral miRNAs, an in depth functional understanding of most virus-encoded miRNAs is lacking. Here we focus on a few viral miRNAs with well-defined functions. We use these examples to extrapolate general themes of viral miRNA activities including autoregulation of gene expression, avoidance of host defenses, and a likely important role in maintaining latent and persistent infections. We hypothesize that although the molecular mechanisms and machinery are similar, the majority of viral miRNAs may utilize a target strategy that differs from host miRNAs. That is, many viral miRNAs may have evolved to regulate viral-encoded transcripts or networks of host genes that are unique to viral miRNAs. Included in this latter category are a likely abundant class of viral miRNAs that may regulate only one or a few principal host genes. Key steps forward for the field are discussed, including the need for additional functional studies that utilize surgical viral miRNA mutants combined with relevant models of infection.

HIV-1 RRE RNA acts as an RNA silencing suppressor by competing with TRBP-bound siRNAs

“…They are present in various amounts in a large number of viruses and they impact cellular functions. 11,66,67 Many described proteins and RNAs acting as RSSs have mostly been shown to increase viral replication in cell lines from different origin than the natural host, although some have been shown in natural host cells. 68 In addition, the induction of RISC proteins upon virus entry has not been shown, pointing to an intrinsic mechanism rather than an inducible pathway.…”

“…21 It could also increase the activity of oncolytic adenoviruses, which would widen their applications. 18 In certain viral infections 11,14 and cancers, 78 RNAi activity is detrimental to the host. In these cases, a global suppression of RNAi may also be beneficial.…”

“…Several studies have shown that RNAi can directly inhibit viral replication while others have demonstrated that viruses can and do utilize cellular and viral miRNAs and RNAi-associated proteins to enhance viral replication. [9][10][11][12][13][14][15] For example, Human Immunodeficiency Virus-1 (HIV-1) is not restricted by RNAi, 16 while adenovirus is severely restricted, which may limit its use as an oncolytic virus. [17][18][19] The apparent absence of RNAi restriction of some viruses could be explained by the counteraction of encoded viral RNA silencing suppressors (RSSs).…”

MicroRNA expression by an oncogenic retrovirus

“…A lthough >250 viral microRNAs (miRNAs) are expressed by a range of nuclear DNA viruses, efforts to identify miRNAs expressed by RNA viruses have so far been in vain (1,2). In PNAS, Kincaid et al (3) report the identification of five miRNAs encoded by the delta retrovirus bovine leukemia virus (BLV) that are expressed in BLV-transformed B cells.…”

“…The pre-miRNA is then exported to the cytoplasm where the mature miRNA is released after cleavage by a second RNase III enzyme, called Dicer. Because the large majority of RNA viruses replicate exclusively in the cytoplasm (the major exceptions to this generalization are retroviruses and orthomyxoviruses), it seemed possible that one reason for the lack of RNA virus miRNAs might be the nuclear localization of the first step in miRNA biogenesis, mediated by Drosha (1,2). However, analysis of the retroviruses HIV type 1 (HIV-1) and human T-cell leukemia virus type 1 (HTLV-1), as well as the orthomyxovirus influenza virus, also failed to reveal any viral miRNA species (7)(8)(9).…”