Polyomaviruses are a family of small DNA viruses widespread among various animal species, including humans. These viruses have a compact, circular, double-stranded DNA genome enclosed within a protein shell called a capsid. In people, these viruses typically establish a lifelong presence after an initial infection, which often occurs without symptoms during childhood, resulting in a latent state.
For individuals with a healthy immune system, the presence of these viruses goes unnoticed, but the situation changes when the immune system is weakened. This allows the dormant virus to reactivate and cause significant health problems.
Common Human Polyomaviruses
While more than a dozen human polyomaviruses have been identified, three are the most studied for their clinical relevance: BK polyomavirus (BKV), JC polyomavirus (JCV), and Merkel cell polyomavirus (MCV). The names for BKV and JCV come from the initials of the first patients from whom the viruses were isolated in 1971. BKV was found in the urine of a kidney transplant recipient, while JCV was discovered in the brain tissue of a patient with a rare neurological disease.
Merkel cell polyomavirus was discovered more recently, in 2008, through genetic sequencing of a rare skin cancer. It is named for its association with Merkel cells, a type of skin cell involved in the sense of touch. These three viruses share a similar genetic structure but infect different tissues and cause distinct diseases upon reactivation.
Transmission and Prevalence
The exact routes of transmission for human polyomaviruses are not perfectly understood but are believed to involve respiratory droplets, the fecal-oral route, and contact with infected urine. For most people, the initial infection is either completely asymptomatic or results in a mild illness often mistaken for a common cold.
Serological studies, which detect antibodies in the blood, demonstrate the high prevalence of these viruses. For BKV and JCV, studies show that a large portion of the adult population has been infected, with seroprevalence rates for BKV reaching 80-90% and for JCV ranging from 40% to 60%. Asymptomatic shedding of the virus, particularly in urine, can occur in healthy individuals, contributing to its spread.
Role in Human Disease
The clinical impact of polyomaviruses arises from the reactivation of a latent virus, which occurs almost exclusively in individuals whose immune systems are significantly weakened. Conditions that lead to this immunocompromised state include:
- Organ transplantation, due to necessary immunosuppressive drugs
- HIV/AIDS
- Certain cancers, such as lymphoproliferative diseases
- Treatment with specific immunomodulatory therapies for autoimmune diseases
Each of the major human polyomaviruses is linked to a distinct disease.
BK polyomavirus is a primary concern for kidney transplant recipients. Its reactivation can lead to polyomavirus-associated nephropathy (PVAN), a condition where the virus attacks and destroys the tubular epithelial cells of the transplanted kidney. This can cause severe graft dysfunction and, if not managed, may result in the loss of the transplanted organ.
JC polyomavirus reactivation is associated with progressive multifocal leukoencephalopathy (PML). In this severe neurological condition, the JC virus infects and destroys oligodendrocytes, the cells responsible for producing myelin. This demyelination disrupts nerve signals in the brain’s white matter, leading to progressive neurological decline. Before the advent of effective antiretroviral therapy, PML was a more common opportunistic infection in patients with AIDS.
Merkel cell polyomavirus functions as an oncovirus, meaning it can contribute to cancer development. It is a causative factor in most cases of Merkel cell carcinoma (MCC), a rare but aggressive skin cancer. In these tumors, the virus’s genetic material integrates into the host cell’s DNA, and viral proteins known as T antigens drive the uncontrolled proliferation of cancer cells.
Diagnosis and Management
When a polyomavirus-associated disease is suspected, molecular techniques are used to confirm the virus’s presence and activity. The most common method is the quantitative polymerase chain reaction (PCR) test, which measures the amount of viral DNA, or viral load, in fluids like blood, urine, or cerebrospinal fluid. Monitoring the viral load is useful for tracking the infection’s activity and response to treatment.
While PCR tests are central to diagnosis, a definitive diagnosis for conditions like PVAN and Merkel cell carcinoma often requires a tissue biopsy. In a biopsy, a small sample of the affected tissue is examined under a microscope for signs of viral infection or cancerous changes. Immunohistochemistry, a staining technique that uses antibodies to detect viral proteins in the tissue, can also confirm the diagnosis.
The management strategies for diseases caused by polyomaviruses are challenging because there are no specific antiviral drugs approved to target BKV or JCV directly. For transplant patients with BKV-associated nephropathy, the primary approach is to carefully reduce the dosage of immunosuppressive medications. This allows the patient’s immune system to regain control and fight the virus but must be balanced against the risk of organ rejection.
For patients with PML caused by JCV, the main goal is to restore immune function. In individuals with HIV, this is achieved through highly active antiretroviral therapy (HAART). In the case of Merkel cell carcinoma, treatment involves standard cancer therapies, including surgery to remove the tumor, radiation therapy, and immunotherapies that help the patient’s immune system attack the cancer cells.