Polyomaviruses

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Chapter 267 Polyomaviruses

Gregory A. Storch

The polyomaviruses are small (45-nm), nonenveloped, double-stranded circular DNA viruses with genomes of approximately 5,000 bp. JC virus and BK viruses infect humans and cause disease. Two other polyomaviruses, designated KI virus and WU virus, can be detected in respiratory samples from children; the role of these viruses as pathogens is still under investigation. A fifth polyomavirus, called Merkel cell polyomavirus, can be detected in tumor tissue from individuals with Merkel cell carcinoma, an unusual neuroectodermal tumor of the skin that occurs primarily in elderly and immunocompromised individuals. A sixth human polyomavirus has been isolated from patients with the dermatologic condition trichodysplasia granulosa. The new virus has been provisionally named Trichodysplasia spinulosa virus. Trichodysplasia granulosa is a condition of the skin that occurs in immunocompromised individuals and involves the development of follicular papules and keratin spines, usually involving the face. JC and BK viruses are closely related to each other, with about 75% genome homology. KI and WU have a similar relationship to each other but are distinct from other human and animal polyomaviruses. Merkel cell polyomavirus is also distinct from the other human polyomaviruses.

JC and BK viruses are tropic for renal epithelium; JC virus also infects brain oligodendrocytes and is the etiologic agent of progressive multifocal leukoencephalopathy (PML), a rare and fatal demyelinating disease of immunocompromised persons, especially those with AIDS. PML has been reported in small numbers of individuals receiving the immunomodulatory agents natalizumab (Tysabri), used to treat multiple sclerosis and Crohn’s disease, and efalizumab (Raptiva), used to treat psoriasis. BK virus is the cause of transplant nephropathy in renal transplant recipients and of hemorrhagic cystitis in hematopoietic stem cell and bone marrow transplant recipients. Several million persons in the USA were exposed to simian virus 40 (SV40), an oncogenic polyomavirus of Asian macaques that shares 70% homology to human polyomaviruses, from contaminated poliovirus vaccines administered during 1955-1963. There were no recognized sequelae and no demonstrable increased risk for cancer.

BK and JC viruses can induce tumors in mice, and polyomavirus sequences have been identified in human tumors, including osteosarcomas, mesotheliomas, and brain tumors (ependymomas, glioblastomas, oligodendrogliomas, and others). An etiologic role for BK and JC polyomaviruses in human oncogenesis has not been confirmed. Genomic sequences from Merkel cell virus have been found integrated in Merkel cell carcinomas, supporting a role in oncogenesis.

Infection with all 5 of the human polyomaviruses appears to be widespread during childhood but is usually asymptomatic. Approximately half of children in the USA are infected with BK virus by 3-4 yr of age and with JC virus by 10-14 yr of age, and approximately 60-80% of adults are seropositive for one or both viruses. Likewise, a high percentage of adults appear to be seropositive for KI, WU, and MC viruses. The KI and WU viruses have been detected in respiratory secretions of 1-9% of young children with symptomatic respiratory illness but are also found in children without acute respiratory illness. Primary BK virus infection in children has been reported with mild upper respiratory tract symptoms rarely and with acute cystitis in 3 children but is generally not recognized clinically. Infection with polyomaviruses is thought to persist throughout life, with JC and BK viruses remaining latent in renal epithelium, oligodendrocytes, and peripheral blood mononuclear cells. The site of latency of the other human polyomaviruses is not currently known. Approximately 30-50% of healthy persons have detectable BK or JC virus in renal tissue at autopsy. Reactivation and viruria occur with increased frequency with advancing age and are more common in immunocompromised persons. On the basis of polymerase chain reaction (PCR) results, BK and JC viruria occurs in 2.6% and 13.2%, respectively, of persons < 30 yr of age and in approximately 9% and 50%, respectively, of persons > 60 yr of age.

Reactivation of BK and JC viruses with asymptomatic viruria occurs in 10-50% of hematopoietic stem cell and bone marrow transplant recipients and in 30% of renal transplant recipients. Of those renal transplant recipients who demonstrate BK viruria, approximately one third also have plasma viremia. Recipients with plasma viremia are at risk for development of nephropathy, which can clinically mimic allograft rejection and can result in failure of the allograft. Reduction of immunosuppression has been effective in preventing progression from viremia to nephropathy, and thus post-transplant monitoring of either urine or plasma by PCR is important. It is particularly important to distinguish BK nephropathy from rejection because the treatments are different—increase in immunosuppression for rejection but decrease in immunosuppression for BK nephropathy.

PCR is the preferred means to detect the BK and JC viruses. The high seroprevalence in the general population and lack of clear relationship to clinical illness limit the usefulness of serologic testing. There are no proven antiviral treatments for BK or JC virus infection, although cidofovir may be effective in some cases of BK-related transplant nephropathy. Effective treatment of AIDS with antiretroviral therapy can prevent the progression of PML.

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