Discovery and function of polyomaviral microRNAs
MetadataShow full item record
Polyomaviruses are small, DNA tumor viruses that establish persistent infections in their natural hosts. Several members of the virus family are associated with human pathologies such as Progressive Multifocal Leukoencephalopathy (PML), trichodysplasia spinulosa and Merkel cell carcinoma. Polyomaviruses are one of the first virus family known to encode miRNAs. These polyomaviral miRNAs are located antisense to the early transcripts and hence, mediate the autoregulation of the viral early proteins, the T antigens. There are two major questions in the field of polyomaviral miRNAs – What is the biological significance of this miRNA-mediated autoregulation of the early transcripts? Are there other biological significant targets for these polyomaviral miRNAs? This work addressed these two questions through an evolutionary approach. First, examination of SV40 and JCV variants indicated the high conservation of the miRNAs and their autoregulatory functions. Second, miRNA-mediated autoregulation of the early transcripts is conserved in a newly discovered, evolutionarily divergent viruses, the Bandicoot papillomatosis and Carcinomatosis viruses (BPCVs). Third, by inspecting divergent members of the polyomavirus family, we have shown that some non-human polyomaviruses encode miRNAs, with the function to autoregulate the early transcripts conserved. The conservation of miRNAs both among variants of individual member and across divergent members of the polyomavirus family implies importance. More importantly, a conserved function of autoregulating the early transcript further emphasized the biological relevance of the miRNAs in polyomavirus biology. Yet, the lack of replicative differences between miRNA-expressing and miRNA-null SV40 strains during lytic infections suggests a role for the polyomaviral miRNAs under a different setting, perhaps in the establishment of persistent infection of their natural hosts. This work represents an evolutionary study of polyomaviral miRNAs that has demonstrated the conserved nature of miRNA-mediated autoregulation of the early transcripts among various members of the polyomavirus and polyoma-like virus families. These results have implicated a potential role for the polyomaviral miRNAs in the establishment of persistent infection and raised the possibility of using the JCV miRNAs as potential biomarkers as a non-invasive form of diagnostic for PML.