Human polyomavirus infection

What is human polyomavirus infection?

Human polyomaviruses (HPyVs) are DNA viruses that establish lifelong latency in the body following a typically asymptomatic primary infection.

In immunocompetent individuals, both the primary and persistent infections are clinically silent and not associated with adverse effects. However, HPyVs can reactivate in immunocompromised states and cause disease.

Out of 14 recognised HPyV species, four have established causal links to disease:

• JC polyomavirus (JCPyV or HPyV2)
• BK polyomavirus (BKPyV or HPyV1)
• Merkel cell virus (HPyV5)
• Trichodysplasia spinulosa polyomavirus (TSPyV or HPyV8).

JC virus and BK virus are the most studied human polyomavirus species.


Who gets human polyomavirus infection?

Human polyomavirus infections are highly prevalent, with adult seroprevalence estimated at 50-90% depending on the species. BK virus is commonly acquired in early childhood, and primary infection for JC virus mainly occurs in childhood or adolescence.

Diseases associated with HPyV predominantly occur in specific immunocompromised cohorts, such as seen with:

• HIV infection
• Haematologic malignancy
• Solid organ transplantation
• Bone marrow transplantation
• Drug-induced immunosuppression.



What causes human polyomavirus infection?

Human polyomaviruses are small, non-enveloped DNA viruses of the Polyomaviridae family that are transmitted human-to-human. Routes of transmission appear to vary with species, with evidence for spread via oral, respiratory, and faecal-oral routes, as well as direct skin contact.

What are the clinical features of human polyomavirus infection? 

Cutaneous features

• Merkel cell carcinoma
  • Rare, aggressive skin cancer associated with oncogenic Merkel cell virus
  • Presents as a painless, firm, raised nodule with a bluish-red hue, typically on photoexposed sites
• Trichodysplasia spinulosa
  • Caused by Trichodysplasia spinulosa polyomavirus
  • Characterised by facial follicular papules with central keratin spikes along with alopecia of the eyebrows and eyelashes
• Pruritic and dyskeratotic dermatosis 
  • Associated with cutaneous HPyV6/7 reactivation 
  • Extremely rare eruption characterised by “peacock plumage” parakeratosis on histology
  • Presents with highly pruritic, brown to grey, scaly or lichenified plaques widespread over the torso and extremities

Non-cutaneous features

• Polyomavirus-associated nephropathy
  • Primarily caused by BK virus, and rarely JC virus, reactivation in kidney transplant patients
  • Presents asymptomatically as a gradual rise in serum creatinine
• Haemorrhagic cystitis 
  • Associated with BK virus following haematopoietic stem cell transplantation
  • Characterised by dysuria, haematuria, and urinary frequency
• Progressive multifocal leukoencephalopathy (PML)
  • Demyelinating disorder caused by JC virus reactivation, seen particularly in patients with HIV/AIDS or receiving natalizumab (monoclonal antibody used to treat multiple sclerosis and Crohn disease)
  • Presents subacutely with progressive focal neurological deficits eg, motor weakness, ataxia, aphasia, visual field defects, personality changes, cognitive impairment 

A Merkel cell carcinoma on the forehead (MCC-patient1)

What are the complications of human polyomavirus infection?

• Metastasis of Merkel cell carcinoma
• Kidney allograft dysfunction and loss in polyomavirus-associated nephropathy
• Urinary blood clots and urinary obstruction secondary to haemorrhagic cystitis 
• Graft rejection or graft-versus-host disease due to therapeutic reductions of immunosuppression
• Permanent neurological damage secondary to PML

How is human polyomavirus infection diagnosed?

In clinical practice, human polyomavirus infection is diagnosed by:

• PCR for viral DNA in blood, urine, or CSF
• Biopsy with immunohistochemistry.

Other HPyV detection methods include:

• Serology
• Cell cultures
• Electron microscopy
• In-situ hybridization. 

What is the differential diagnosis for human polyomavirus infection?

Polyomavirus-associated nephropathy

• Acute transplant rejection
• Interstitial nephritis due to drug hypersensitivity
• Other viral infection eg, cytomegalovirus (CMV), herpes simplex virus (HSV), adenovirus

BKPyV-associated haemorrhagic cystitis

• Urothelial neoplasms eg, flat urothelial carcinoma in situ
• Chemotherapy and radiation-related haemorrhagic cystitis

Progressive multifocal leukoencephalopathy

• Other brain infection eg, CMV encephalitis, HSV encephalitis, neurotoxoplasmosis, HIV encephalopathy 
• CNS lymphoma
• Progression of multiple sclerosis

Merkel cell carcinoma

• Basal cell carcinoma
• Squamous cell carcinoma
• Amelanotic melanoma
• Angiosarcoma
• Pyogenic granuloma
• Epidermal cyst
• Cutaneous B-cell or T-cell lymphoma 
• Cutaneous metastasis

Trichodysplasia spinulosa

• Lichen spinulosus
• Trichostasis spinulosa
• Keratosis pilaris atrophicans faciei
• Follicular hyperkeratotic spicules (associated with multiple myeloma)

What is the treatment for human polyomavirus infection?

There are no known effective antiviral agents against human polyomaviruses. Treatment for HPyV-associated disease centres on:

• Reducing immunosuppression
  • In the case of HIV-positive patients, immune reconstitution with highly active anti-retroviral therapy (HAART) is the mainstay of treatment for progressive multifocal leukoencephalopathy 
• Supportive care
• Specialist input eg, urgent renal team input for kidney transplant patients.



See pages on Merkel cell carcinoma and trichodysplasia spinulosa for details on their treatment.

How do you prevent human polyomavirus infection?

There is no way to prevent human polyomavirus infections. The risk of certain HPyV-associated diseases can be mitigated by monitoring viral load and making cautious dose reductions of immunosuppressive agents.

What is the outcome for human polyomavirus infection?

Human polyomavirus infections are largely harmless in immunocompetent individuals, but in immunocompromised patients can cause disease associated with significant morbidity and mortality.

Prognosis depends on the HPyV-associated disease:

• PML is often fatal, with an overall mortality rate of 30-50% within the first few months; in HIV-positive individuals, treatment with HAART improves the one-year survival rate from 10% to 50%.
• Merkel cell carcinoma outcomes depend on the stage at diagnosis; an estimated 75% of people with localised disease live for at least five years after diagnosis.
• BK virus-associated nephropathy historically led to graft failure in 50% of patients within 2 years of diagnosis, though graft survival rates have improved with serial monitoring and early reduction of immunosuppression.
• BK virus-associated haemorrhagic cystitis usually resolves spontaneously with supportive care.
• Trichodysplasia spinulosa is benign and tends to slowly self-resolve.