The functions of herpesvirus-encoded microRNAs

Abstract

Bioinformatic and direct cloning approaches have led to the identiWcation of over 100 novel miRNAs expressed in DNA viruses, although the function of the majority of these small regulatory RNA molecules is unclear. Recently, a number of reports have now identiWed potential targets of viral miRNAs, including cellular and viral genes as well as an ortholog of an important immunoregulatory cellular miRNA. In this review, we will cover the identiWcation and characterization of miRNAs expressed in the herpesvirus family and discuss the potential signiWcance of their role in viral infection.

Human herpesvirus miRNAs statistically preferentially target host genes involved in cell signaling and adhesion/junction pathways

“…Previous reports indicated that some viruses modulate host immune and apoptosis-related pathways, mostly as a kind of immunoevasion strategy [1,3,8]. Our statistical npg findings were consistent with these reports, while suggesting additional new signaling pathways.…”

“…Ninety-five mature human viral miRNAs have been reported so far, eighty-five of which are encoded by five large double-stranded DNA human herpesviruses, including human cytomegalovirus (HCMV), Epstein-Barr virus (EBV), herpes simplex virus 1 (HSV-1), HSV-2 and Kaposi's sarcoma-associated herpesvirus (KSHV) [2]. Studies of individual human viral miRNAs have shown that they can regulate both viral and human genes to suppress host anti-viral response and modify behaviors of infected cells [1,3]. However, to date, there has been no systematic study of whether viral miRNAs preferentially target any particular pathways in human.…”

Viral epigenomes in human tumorigenesis

“…EBVencoded miRNAs regulate both host and viral genes, hence an investigation of these relationships is very important for our understanding of the biological processes involved in viral latency, which could be exploited to design strategies for combating potential harm to the host (Pfeffer et al, 2004;Nair and Zavolan, 2006;Scaria et al, 2006;Gottwein and Cullen, 2008). In this regard, the interactions between BART miRNAs, such as miR-BART16, and LMP1, the most oncogenic known gene in EBV (Table 1), have been demonstrated (Grey et al, 2008;Cullen, 2009 …”

Small RNA profiling reveals antisense transcription throughout the KSHV genome and novel small RNAs

“…miRNAs have been the subject of enormous interest due to the regulatory roles they play in numerous and disparate biological processes, including viral infection (for review, see Nair and Zavolan 2006;Samols and Renne 2006;Sarnow et al 2006;Gottwein and Cullen 2008;Grey et al 2008;Pfeffer 2008;Sullivan 2008). miRNAs are small, z22-nucleotide (nt) RNAs that bind to mRNAs and regulate gene expression in a posttranscriptional manner (for review, see Bartel 2004;Kim 2005;Vasudevan et al 2008).…”

“…However, some viruses encode miRNAs within their genomes. Viral miRNAs have been identified from viruses with DNA genomes, including those of the Herpes, Polyoma, and Asco virus families (Nair and Zavolan 2006;Samols and Renne 2006;Gottwein and Cullen 2008;Grey et al 2008;Hussain et al 2008;Sullivan 2008;Sullivan and Cullen 2009). Most viral miRNAs have been identified by sequencing of small RNA libraries (Pfeffer et al 2004;Cai et al 2005Dunn et al 2005;Samols et al 2005; Burnside et al 2006;Dolken et al 2007;Yao et al 2007; Umbach et al 2008), but computational methods have played a key role in the discovery of numerous viral miRNAs (Grey et al 2005;Pfeffer et al 2005;Cui et al 2006;Grundhoff et al 2006;Buck et al 2007;Sullivan and Grundhoff 2007;Hussain et al 2008;Seo et al 2008).…”