Human polyomavirus 7

Human polyomavirus 7 (HPyV7) is a small non-enveloped DNA virus that forms part of the normal flora of human skin and, in almost everyone, causes no disease at all. It is included in the atlas for completeness and because, in a small number of profoundly immunosuppressed patients, it has been linked to an unusual itchy skin eruption. Discovered in 2010 from the skin of healthy adults, it is one of the deltapolyomaviruses, the genus that also contains the closely related HPyV6, and like the other human polyomaviruses it is acquired silently in childhood and carried for life. Its clinical importance is slight, lying between the harmless respiratory polyomaviruses on the one hand and the disease-causing JC, BK, Merkel cell and trichodysplasia spinulosa viruses on the other.

Discovery and historical significance

HPyV7 was identified in 2010 by Schowalter and colleagues, who detected it, together with the related HPyV6, by rolling-circle amplification of DNA from the skin of healthy volunteers. The two viruses are the commonest polyomaviruses of human skin and were recognised from the outset as components of the normal skin virome rather than as agents of disease, part of a wider appreciation in the years after 2007 that the human polyomaviruses are far more numerous than the two classical pathogens, BK and JC, and that most are harmless residents of the skin, gut or respiratory tract. For several years HPyV7 had no disease association at all. Later reports linking it to a rare skin eruption in immunosuppressed patients gave it a tentative clinical significance, but it remains, for practical purposes, a commensal.

Classification, structure, and genome

The virus belongs to the family Polyomaviridae, genus Deltapolyomavirus, with the current International Committee on Taxonomy of Viruses species name Deltapolyomavirus septihominis (formerly Human polyomavirus 7). The genus Deltapolyomavirus contains the human polyomaviruses 6, 7, 10 and 11, the human skin and gut commensals distinct from the alpha- and betapolyomaviruses that include the major pathogens. Structurally it is a typical polyomavirus: a non-enveloped icosahedral particle about 40 to 45 nanometres across, built from 72 pentamers of VP1, with a circular double-stranded DNA genome of about 5,000 base pairs encoding the early and late proteins.

Replication cycle

After silent childhood infection the virus persists on the skin and follows the standard polyomavirus replication cycle: attachment and entry, delivery of the genome to the nucleus, expression of the early genes, large T antigen driving the cell into S phase, replication of the genome, and assembly and release of progeny virions. In the rare skin disease attributed to it the virus is found replicating productively in epidermal keratinocytes.

Pathogenesis

In the overwhelming majority of people HPyV7 is a harmless resident of the skin and causes no pathology. The rare disease attributed to it occurs only in profoundly immunosuppressed patients, in whom uncontrolled productive replication in the epidermis is associated with a hyperproliferative, itchy eruption. As with the other human polyomaviruses, disease reflects a failure of the cellular immunity that normally keeps replication in check rather than any change in the virus. Its behaviour places it between the wholly harmless respiratory and gut polyomaviruses and the established pathogens: capable, under extreme immunosuppression, of a productive proliferative skin infection, but without the integration and transformation that drive Merkel cell carcinoma or the renal and neurological disease of BK and JC viruses.

Epidemiology

HPyV7 is common and globally distributed, with adult seroprevalence on the order of 55 per cent and acquisition in childhood. It is detectable on the skin of many healthy people, where its presence carries no clinical significance. The associated skin disease is exceedingly rare, reported only in a handful of immunosuppressed patients.

Natural history

The natural history is that of a lifelong skin commensal: silent primary infection in childhood, then persistent harmless carriage. In the immunocompetent host nothing further happens, and only sustained immunosuppression has been associated with the rare proliferative skin disease.

Clinical presentations and complications

HPyV7 has no recognised disease in immunocompetent people. In a small number of immunosuppressed patients, notably lung transplant recipients and people with chronic lymphocytic leukaemia, it has been associated with a pruritic, brown, plaque-like or papular hyperproliferative eruption, typically on the trunk and limbs. On biopsy the lesions show abundant viral protein in the epidermal keratinocytes with a distinctive cytopathic change, and abundant viral DNA is present, which is the basis for attributing the eruption to the virus rather than treating its detection as incidental. The condition is itchy and cosmetically troublesome but not dangerous, it does not become malignant, and the association, while supported by the presence of replicating virus in the lesions, still rests on few reported cases.

Diagnosis

Because finding the virus on normal skin means nothing, diagnosis of the rare HPyV7-associated eruption rests on a skin biopsy showing a characteristic viral cytopathic change in the keratinocytes, with the virus then confirmed in the lesion by PCR or immunohistochemistry. There is no role for routine testing for the virus outside this specific clinical question.

Management

There is no specific antiviral treatment. Management of the rare skin disease follows the polyomavirus principle of restoring immune control by reducing immunosuppression where the underlying condition permits, with otherwise supportive care of the skin. Improvement tends to follow the recovery of immune function.

Prevention and public health

Vaccination

There is no vaccine, and none is warranted: the virus is a near-universal, generally harmless skin commensal, so there is neither a means of preventing infection nor a public-health reason to attempt it.

South African context

HPyV7 has no specific South African epidemiological data and no surveillance, and the skin disease attributed to it is vanishingly rare. Its only local relevance is that the eruption could in principle be encountered in the immunosuppressed patients cared for by transplant and haematology services, where it would be recognised on biopsy and managed by adjusting immunosuppression.