Abstract
The genomes of polyomaviruses are characterized by their tripartite organization with an early region, a late region and a noncoding control region (NCCR). The early region encodes proteins involved in replication and transcription of the viral genome, while expression of the late region generates the capsid proteins. Transcription regulatory sequences for expression of the early and late genes, as well as the origin of replication are encompassed in the NCCR. Cell tropism of polyomaviruses not only depends on the appropriate receptors on the host cell, but cell-specific expression of the viral genes is also governed by the NCCR. Thus far, 15 polyomaviruses have been isolated from humans, though it remains to be established whether all of them are genuine human polyomaviruses (HPyVs). The sequences of the NCCR of these HPyVs show high genetic variability and have been best studied in the human polyomaviruses BK and JC. Rearranged NCCRs in BKPyV and JCPyV, the first HPyVs to be discovered approximately 30 years ago, have been associated with the pathogenic properties of these viruses in nephropathy and progressive multifocal leukoencephalopathy, respectively. Since 2007, thirteen novel PyVs have been isolated from humans: KIPyV, WUPyV, MCPyV, HPyV6, HPyV7, TSPyV, HPyV9, HPyV10, STLPyV, HPyV12, NJPyV, LIPyV and QPyV. This review describes all NCCR variants of the new HPyVs that have been reported in the literature and discusses the possible consequences of NCCR diversity in terms of promoter strength, putative transcription factor binding sites and possible association with diseases.
Highlights
BKPyV, JCPyV, Karolinska Institute polyomavirus (KIPyV), WUPyV, Merkel cell PyV (MCPyV), HPyV6, HPyV, Trichodisplasia spinulosa PyV (TSPyV), HPyV9, HPyV10, Saint Louis PyV (STLPyV), HPyV12, and New Jersey PyV (NJPyV) are classified as human polyomaviruses by the International Committee of Taxonomy of Viruses [19,20], Lyon IARC PyV (LIPyV) has only been very recently described, while LIPyV DNA was originally detected in human skin [17]
We provide an overview of the mutations in the noncoding control region (NCCR), which is defined as the sequence between the start codon of the large T-antigen (LT)/small t-antigen (sT) gene and the start codon of the VP2 gene, of the novel HPyVs and their known effect on promoter activity
Similar to BKPyV and JCPyV, novel HPyV isolates with mutations in their NCCR are commonly detected in human samples
Summary
Polyomaviruses (PyVs) are non-enveloped viruses that are typically 40–45 nm in diameter, and that possess a double-stranded circular genome of around 5000 base-pairs. BKPyV, JCPyV, KIPyV, WUPyV, MCPyV, HPyV6, HPyV, TSPyV, HPyV9, HPyV10, STLPyV, HPyV12, and NJPyV are classified as human polyomaviruses by the International Committee of Taxonomy of Viruses [19,20], LIPyV has only been very recently described, while LIPyV DNA was originally detected in human skin [17]. Despite its original identification in human liver, gastro-intestinal tract and colon tissue and a VP1 seropositivity (respectively LT seropositivity) between ~20–90% (respectively 30–40%) in healthy adults or malignant and non-malignant gastro-intestinal tract patients [15,25], HPyV12 DNA could not be detected in numerous human samples from different sources [22,26,27,28,29,30]. HPyV12 positive samples were contaminated [32]
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