Abstract
Although >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. Interestingly, BLV uses RNA polymerase III (pol III) to directly transcribe the pre-miRNA hairpins that give rise to these viral miRNAs, thereby preventing the cleavage of viral genomic RNA and mRNA species as a result of pre-miRNA excision. Moreover, one of the BLV miRNAs, miR-B4, shares the same seed sequence as cellular miR-29 and therefore can down-regulate many of the same mRNA targets. As miR-29 overexpression can induce chronic lymphocytic leukemia (CLL) in transgenic mice (4), and BLV induces CLL-like B-cell neoplasms in infected cattle and sheep (5), it appears likely that these viral miRNAs play an important role in BLV pathogenesis.
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