Polyomavirus Infections of Humans

Abstract

Research on polyomaviruses began in 1953 when Ludwik Gross isolated a filterable agent that induced tumours in newborn mice. This agent became the archetypal member of the Polyomaviridae family. In 1971, JC virus and BK virus were reported and named after the patients’ initials. More than 30 years passed before the Karolinska Institute virus and Washington University virus were identified from respiratory samples in paediatric patients. The Merkel cell polyomavirus was identified in 2008 for its association with the aggressive Merkel cell carcinoma skin cancer. Recently, polyomaviruses 6, 7, 9 and the trichodysplasia spinulosa‐associated polyomavirus have been discovered. Along with simian virus 40, which has been associated with human disease, there are now 10 polyomaviruses relevant to humans. The range of diseases associated with these human polyomaviruses shows that they are significant causes of human infections. The accumulated knowledge gained from the study of each individual virus helps to understand each in their particular niche.

Key Concepts:

  • Polyomaviruses are DNA viruses.

  • Polyomaviruses cause significant human infections, especially in the immunocompromised population.

  • Human infection most likely occurs during childhood.

  • Haemorrhagic cystitis and polyomavirus‐associated nephropathy are significant clinical entities caused by the BK virus in solid organ transplant recipients.

  • Progressive multifocal encephalopathy is a fatal demyelinating disease caused by the JC virus.

  • Merkel cell virus and SV40 are potential oncogenic agents.

  • Treatment is supportive and an effective antiviral agent has not been identified so far.

Keywords: polyomavirus; human polyomavirus infections; polyomavirus nephropathy; haemorrhagic cystitis; progressive multifocal leukoencephalopathy; trichodysplasia spinulosa; Merkel cell carcinoma; polyomavirus 6 and 7; human polyomavirus 9; KI and WU polyomavirus

Figure 1.

Schematic presentation of the circular double stranded DNA genome of HPyV. The gene products encoded by the early region (LT‐ag and S‐t ag) and the late region (agnoprotein, capsid proteins VP1, VP2 and VP3) are indicated. The noncoding control region (NCCR), consisting of the origin of replication (Mischitelli et al., ) and the transcription control region (TCR), is interspersed between the early and late region. The NCCR controls viral DNA replication and transcription of the early and late genes.

Figure 2.

Receptors for PyV are not known, but appear to contain sialic acid. Virions are taken up by endocytosis and are transported to the nucleus by interaction of endocytic vacuoles with the cytoskeleton. Uncoating occurs inside the nucleus. Inside the nucleus, the virus mini‐chromosome (genome–histone complex) is transcribed by host cell RNA polymerase II to produce early messenger ribonucleic acids (mRNAs). The early region proteins are the T‐antigens. After DNA replication has occurred, transcription of the late genes occurs from the late promoter and results in the synthesis of the structural proteins, VP1, VP2 and VP3. Assembly occurs in the nucleus. Some virus particles are exported to the cell surface in cytoplasmic vacuoles. The remaining virus is released when the cell lyses. The complete replication cycle takes 48–72 h, depending on the multiplicity of the infection.

Figure 3.

Phylogenetic analysis of polyomavirus LT, ST, VP1 and VP2 protein sequences. The analysis includes: human polyomaviruses (BKV, JCV, KIV, WUV and MCV, all marked with a green rectangle). (From Feng et al., ; Figure 2B, reproduced with permission from The American Association for the Advancement of Science.)

Figure 4.

Clinical appearance and histology of the trichodysplasia spinulosa patient. Facial appearance at presentation is shown in (a). Note the thickened skin, particularly on the nose and in the eyebrow region accompanied by central alopecia. Apart from the eyebrows and nose, papules are seen on the cheeks, chin, forehead and ears. Especially on the nose, but occasionally also in cheeks and chin, keratotic spicules protruded from the enlarged follicular orifices. (b) A close‐up of the nose at presentation with numerous papules and spicules. (c) A section of a formalin‐fixed, paraffin‐embedded biopsy of a hyperkeratotic follicular papule from the forehead. The epidermis reveals enlarged, hyperplastic hair bulbs and hypercornification within a distended follicular infundibulum (HE stain, 10×). (d) A detail of the nose 3 months after topical cidofovir treatment. Papules and spicules have largely resolved and hairs have regained growth. (From van der Meijden, E. PLoS Pathog 6(7): e1001024.)

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Further Reading

Ahsan N (ed.) (2006) Polyomaviruses and Human Diseases, vol. 577. New York, NY: Springer Science + Business Media.

Bohl DL and Brennan DC (2007) BK virus nephropathy and kidney transplantation. Clinical Journal of the American Society of Nephrology 2(suppl. 1): S36–S46.

Brennan DC (2011) Clinical manifestations and diagnosis of BK virus‐induced (polyomavirus‐induced) nephropathy in kidney transplantation. http://www.uptodate.com

Brennan DC, Agha I, Bohl DL et al. (2005) Incidence of BK with tacrolimus versus cyclosporine and impact of preemptive immunosuppression reduction. American Journal of Transplantation 5(3): 582–594.

Khalili K and Stoner GL (eds) (2001) Human Polyomaviruses: Molecular and Clinical Perspectives. New York, NY: Wiley‐Liss Inc.

Randhawa P and Brennan DC (2006) BK virus infection in transplant recipients: an overview and update. American Journal of Transplantation 6(9): 2000–2005.

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Java, Anuja, Cheng, Xingxing, and Brennan, Daniel C(Apr 2012) Polyomavirus Infections of Humans. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0023619]