Abstract
Retroviruses are not expected to encode miRNAs because of the potential problem of self-cleavage of their genomic RNAs. This assumption has recently been challenged by experiments showing that bovine leukemia virus (BLV) encodes miRNAs from intragenomic Pol III promoters. The BLV miRNAs are abundantly expressed in B-cell tumors in the absence of significant levels of genomic and subgenomic viral RNAs. Using deep RNA sequencing and functional reporter assays, we show that miRNAs mediate the expression of genes involved in cell signaling, cancer and immunity. We further demonstrate that BLV miRNAs are essential to induce B-cell tumors in an experimental model and to promote efficient viral replication in the natural host.
Highlights
Encoded miRNAs were first identified in DNA viruses
The miRNA copy numbers measured in primary peripheral blood mononuclear cell (PBMC) from wild-type infected calves (Bo-WT) were similar to the levels of BL3 cells transduced with a lentiviral vector expressing the bovine leukemia virus (BLV) miRNAs (BL3-miRNA, Fig 1C)
We have provided mechanistic and functional evidence demonstrating that the BLV miRNAs modify host gene expression to promote viral persistence and induce pathogenicity
Summary
Encoded miRNAs were first identified in DNA viruses. Most of these miRNAs are generated from endonucleolytic cleavage of long viral transcripts. BLV miRs Promote Viral Replication and Malignancy. Recherche” and the “Plan Cancer” of the “Service Public Fédéral” and the Polish National Science Centre (decision 2012/07B/NZ6/03536). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript
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