All members of this virus subfamily have the capacity to transform normal cells in culture and to induce tumors in species other than those in which they are normally found in nature. “Polyoma” means many (poly-) tumor (-oma). However, Polyomavirus has not yet been shown to cause tumors in humans. There are three human polyomaviruses: BK, JC, and Merkel cell polyomaviruses (BKV, JCV, and MCV, respectively). JCV has been associated with progressive multifocal leukoencephalopathy (PML), a rare, fatal, demyelinating disease that occurs only in patients with impaired immune function (for example, those with AIDS). BKV can cause cystitis in this same population. MCV was discovered in 2008 by molecular technologies. MCV DNA can be detected in the majority of cases of Merkel cell carcinoma, a rare and aggressive form of skin cancer.

A. Epidemiology and pathogenesis

 The human polyomaviruses BKV and JCV are transmitted by droplets from the upper respiratory tract of infected persons and, possibly, through contact with their urine. Infection with these viruses usually occurs in childhood. Specific antibody to one or both human polyomaviruses is present in 70 to 80 percent of the adult population. There is evidence that both BKV and JCV spread from the upper respiratory tract to the kidneys, where they may persist in an inactive state in the tubular epithelium of healthy individuals. Polyomaviruses follow the basic pattern of DNA virus genome replication and gene expression in the nucleus. The enzymes and precursors synthesized in preparation for cellular DNA synthesis are made available for syn thesis of viral DNA. This productive cycle leads to viral multiplication and, ultimately, to death of the host cell.

B. Clinical significance

Immune compromise of various types can be associated with the development of PML, so named because the lesions are restricted to white matter (Figure 1). PML, thought to be caused by reactivated JCV that has entered the central nervous system via the blood, occurs as a complication of a number of lymphoproliferative disorders and chronic diseases that affect immune competence. [Note: In recent years, PML has been seen especially in patients with AIDS.] In PML, JCV carries out a cytocidal infection of the brain, specifically of oligodendrocytes, leading to demyelination resulting from myelinated cells losing their capacity to maintain their myelin sheaths. Early development of impaired speech and mental capacity is rapidly followed by paralysis and sensory abnormalities, with death commonly occurring within 3 to 6 months of onset of the initial symptoms. [Note: BKV is also found in the urine (Figure 2) but rarely has pathologic consequences except in immunocompromised patients, who may develop hemorrhagic cystitis.] Merkel cell carcinomas are relatively rare, but aggressive, and develop more frequently in older individuals. These carcinomas also develop more often in persons who are immunocompromised due to AIDS or other immunodeficiency or following organ transplant.

Fig1. Location and properties of polyoma virus infections. JCV = JC polyoma virus; BKV = BK polyomavirus.

Fig2. Electron micrograph of BK virions from the urine of an infected patient.

C. Laboratory identification

Because most people have antibodies to these viruses, serologic techniques are not generally useful in the diagnosis of acute infections. Identification by DNA hybridization of BKV in the urine or JCV in PML lesions in brain tissue is the most sensitive and specific technique for diagnosis of these infections. MCV viral DNA and protein antigens can be detected by molecular techniques in Merkel cell tumors.

D. Treatment and prevention

No successful, specific, antiviral therapy is available. Because polyomavirus infection is nearly universal and asymptomatic, and PML represents reactivation of “latent” virus, there are currently no viable preventive measures.

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مواضيع ذات صلة

Effects of viral infection on the host cell

Assembly and release of progeny viruses

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Polyomavirus-associated nephropathy (PVAN)

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Pathogenesis of Human Papillomavirus

Clinical Syndromes of EBV

EBV Life Cycle

Epstein–Barr virus

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