Characterization of microRNAs encoded by the bovine herpesvirus 1 genome

Glazov, Evgeny A.; Horwood, Paul F.; Assavalapsakul, Wanchai; Kongsuwan, Kritaya; Mitchell, Richard R.; Mitter, Neena; Mahony, Timothy J.

doi:10.1099/vir.0.014290-0

Cited by 45 publications

(56 citation statements)

References 45 publications

(36 reference statements)

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“…Indeed, the entire 122-nt BFV pri-miRNA sequence is fully conserved, with the exception of two nucleotides in the terminal loop of the miR-BF2 stem-loop that, based on previous work (31), are not predicted to affect miRNA processing or expression. Interestingly, comparison of the three highly expressed BFV miRNAs with known viral and cellular miRNAs revealed that the entire miR-BF1-5p seed sequence (nt 2 to 8) is conserved in miR-B5, which is expressed by bovine herpesvirus 1 (BHV-1) in infected cells (38). However, as the mRNA targets for miR-B5 are not currently known, this conservation is not currently informative as to miR-BF1-5p function.…”

Section: Discussionmentioning

confidence: 99%

Identification of Novel, Highly Expressed Retroviral MicroRNAs in Cells Infected by Bovine Foamy Virus

Whisnant

Kehl

Bao

et al. 2014

J Virol

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While numerous viral microRNAs (miRNAs) expressed by DNA viruses, especially herpesvirus family members, have been reported, there have been very few reports of miRNAs derived from RNA viruses. Here we describe three miRNAs expressed by bovine foamy virus (BFV), a member of the spumavirus subfamily of retroviruses, in both BFV-infected cultured cells and BFV-infected cattle. All three viral miRNAs are initially expressed in the form of an ϳ122-nucleotide (nt) pri-miRNA, encoded within the BFV long terminal repeat U3 region, that is subsequently cleaved to generate two pre-miRNAs that are then processed to yield three distinct, biologically active miRNAs. The BFV pri-miRNA is transcribed by RNA polymerase III, and the three resultant mature miRNAs were found to contribute a remarkable ϳ70% of all miRNAs expressed in BFV-infected cells. These data document the second example of a retrovirus that is able to express viral miRNAs by using embedded proviral RNA polymerase III promoters. IMPORTANCE Foamy viruses are a ubiquitous family of nonpathogenic retroviruses that have potential as gene therapy vectors in humans.Here we demonstrate that bovine foamy virus (BFV) expresses high levels of three viral microRNAs (miRNAs) in BFV-infected cells in culture and also in infected cattle. The BFV miRNAs are unusual in that they are initially transcribed by RNA polymerase III as a single, ϳ122-nt pri-miRNA that is subsequently processed to release three fully functional miRNAs. The observation that BFV, a foamy virus, is able to express viral miRNAs in infected cells adds to emerging evidence that miRNA expression is a common, albeit clearly not universal, property of retroviruses and suggests that these miRNAs may exert a significant effect on viral replication in vivo. M icroRNAs (miRNAs) are a diverse class of ϳ22-nucleotide (nt) regulatory RNAs that are expressed by all known multicellular eukaryotes (1). Cellular miRNAs are normally transcribed by RNA polymerase II (Pol II) to give rise to a long primiRNA that is cleaved in the nucleus by the microprocessor complex, consisting of the RNase III enzyme Drosha and the RNA-binding cofactor DGCR8, to release the ϳ60-nt pre-miRNA intermediate, which contains an ϳ22-bp imperfect stem with an ϳ2-nt 3= overhang (2). The pre-miRNA is then exported to the cytoplasm, where it is cleaved by a second RNase III enzyme, Dicer, which removes the terminal loop, leaving a second ϳ2-nt 3= overhang.

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Section: Discussionmentioning

confidence: 99%

Identification of Novel, Highly Expressed Retroviral MicroRNAs in Cells Infected by Bovine Foamy Virus

Whisnant

Kehl

Bao

et al. 2014

J Virol

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“…The identification of an abundant transcript of 60 to 65 nt expressed from the OriLyt could be reminiscent of other viral pre-miRNAs recently identified to be expressed from the OriLyt regions of MCMV (8,17), RCMV (35), bovine herpesvirus (BoHV) (22), and HSV-1/2 (30). However, similar to our results, none of the miRNAs reported in these papers were reported conclusively to be in Ago2 RNA; hence, herpesvirus origin-derived small RNAs represent an area of research that clearly deserves further investigation.…”

Section: Downloaded Frommentioning

confidence: 99%

Small RNA Deep Sequencing Identifies MicroRNAs and Other Small Noncoding RNAs from Human Herpesvirus 6B

Tuddenham

Jung

Chane-Woon-Ming

et al. 2012

J Virol

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Roseolovirus, or human herpesvirus 6 (HHV-6), is a ubiquitous human pathogen infecting over 95% of the population by the age of 2 years. As with other herpesviruses, reactivation of HHV-6 can present with severe complications in immunocompromised individuals. Recent studies have highlighted the importance of herpesvirus-derived microRNAs (miRNAs) in modulating both cellular and viral gene expression. An initial report which computed the likelihood of various viruses to encode miRNAs did not predict HHV-6 miRNAs. To experimentally screen for small HHV-6-encoded RNAs, we conducted large-scale sequencing of Sup-T-1 cells lytically infected with a laboratory strain of HHV-6B. This revealed an abundant, 60-to 65-nucleotide RNA of unknown function derived from the lytic origin of replication (OriLyt) that gave rise to smaller RNA species of 18 or 19 nucleotides. In addition, we identified four pre-miRNAs whose mature forms accumulated in Argonaute 2. In contrast to the case for other betaherpesviruses, HHV-6B miRNAs are expressed from direct repeat regions (DR L and DR R ) located at either side of the genome. All miRNAs are conserved in the closely related HHV-6A variant, and one of them is a seed ortholog of the human miRNA miR-582-5p. Similar to alphaherpesvirus miRNAs, they are expressed in antisense orientation relative to immediateearly open reading frames (ORFs) and thus have the potential to regulate key viral genes.

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“…However the differential expression of miRNA has been shown to correlate with the virulence potential of GaHV-1 field strains [27]. While miRNA expressed by BoHV-1 have been identified how expression might varying across the know subtypes or between field strains is yet to be explored [50]. As NGS costs continue to fall there is likely to be increased usage in veterinary studies and as this knowledge base increases it will undoubted lead to improved understanding of disease development and the role of viral genes in this process.…”

Section: Next Generation Sequencing (Ngs)mentioning

confidence: 97%

“…Further there have been no reports investigating the role miRNA expression, either from the host or pathogen perspectives, with respect to BoHV-1 virulence. Glazov et al [50] reported the BoHV-1 miRNA profile in cultured cells. In a separate report Glazov et al [51] reported changes in expression patterns of bovine miRNA in cultured bovine cells infected with BoHV-1 compared to uninfected cells.…”

Section: Vaccination Against Brdmentioning

confidence: 98%

Understanding the molecular basis of disease is crucial to improving the design and construction of herpesviral vectors for veterinary vaccines

Mahony

2015

Vaccine

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Characterization of microRNAs encoded by the bovine herpesvirus 1 genome

Cited by 45 publications

References 45 publications

Identification of Novel, Highly Expressed Retroviral MicroRNAs in Cells Infected by Bovine Foamy Virus

Identification of Novel, Highly Expressed Retroviral MicroRNAs in Cells Infected by Bovine Foamy Virus

Small RNA Deep Sequencing Identifies MicroRNAs and Other Small Noncoding RNAs from Human Herpesvirus 6B

Understanding the molecular basis of disease is crucial to improving the design and construction of herpesviral vectors for veterinary vaccines

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