The rapidly expanding family of human polyomaviruses: recent developments in understanding their life cycle and role in human pathology

Abstract

Since their discovery in 1971, the polyomaviruses JC (JCPyV) and BK (BKPyV), isolated from patients with progressive multifocal leukoencephalopathy and polyomavirus-associated nephropathy, respectively, remained for decades as the only known members of the Polyomaviridae family of viruses of human origin. Over the past five years, the application of new genomic amplification technologies has facilitated the discovery of several novel human polyomaviruses (HPyVs), bringing the present number to 10. These HPyVs share many fundamental features in common such as genome size and organization. Infection by all HPyVs is widespread in the human population, but they show important differences in their tissue tropism and association with disease. Much remains unknown about these new viruses. In this review, we discuss the problems associated with studying HPyVs, such as the lack of culture systems for the new viruses and the gaps in our basic understanding of their biology. We summarize what is known so far about their distribution, life cycle, tissue tropism, their associated pathologies (if any), and future research directions in the field.

Figure 1. Human polyomaviruses and associated diseases.

A schematic representation of the human body showing the organs to which each human polyomavirus has tropism and causes disease.

Figure 2. Transforming proteins produced by the early region of human polyomaviruses.

A schematic of the early region of human polyomaviruses showing the various protein motifs including conserved region 1 (CR1), the DNAJ domain, the protein phosphatase-2A binding site, the retinoblastoma protein binding site, the region involved in DNA replication, and the p53 binding site. All 10 HPyV produce large T-antigen (T-Ag) and small t-antigen (t-Ag). In addition, MCPyV and JCPyV produce additional splice variants, T4 and the T's, respectively. In Merkel call carcinoma, MCPyV is found integrated in such a way as to cause targeted disruption of T-Ag as indicated by the labeled “truncation region,” which was defined by sequencing the T-Ag genes from multiple MCC (22). Note that truncation at this region preserves the pRb site but not the p53 site or DNA replication region as discussed in the text. The 17kT variants of BKPyV and MCPyV are not shown.