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Progressive Multifocal Leukoencephalopathy: Endemic Viruses and Lethal Brain Disease
Sheila A Haley1, Walter J Atwood1
1Department of Molecular Biology, Cell Biology, and Biochemistry, Brown University, Providence, Rhode Island 02912; email: sheila_haley@brown.edu , walter_atwood@brown.edu.
Abstract:
In 1971, the first human polyomavirus was isolated from the brain of a patient who died from a rapidly progressing demyelinating disease known as progressive multifocal leukoencephalopathy. The virus was named JC virus after the initials of the patient. In that same year a second human polyomavirus was discovered in the urine of a kidney transplant patient and named BK virus. In the intervening years it became clear that both viruses were widespread in the human population but only rarely caused disease. The past decade has witnessed the discovery of eleven new human polyomaviruses, two of which cause unusual and rare cancers. We present an overview of the history of these viruses and the evolution of JC polyomavirus-induced progressive multifocal leukoencephalopathy over three different epochs. We review what is currently known about JC polyomavirus, what is suspected, and what remains to be done to understand the biology of how this mostly harmless endemic virus gives rise to lethal disease.
Insights
Human polyomaviruses, including JC virus, are common but usually harmless. Recent discoveries highlight their role in rare cancers and the evolution of JC virus-associated progressive multifocal leukoencephalopathy.
Area of Science:
- Virology
- Neuroscience
- Oncology
Background:
- Human polyomaviruses, such as JC virus (JCV) and BK virus (BKV), are widespread globally.
- Initially discovered in 1971, JCV causes progressive multifocal leukoencephalopathy (PML), a rare demyelinating disease.
- Over eleven new human polyomaviruses have been identified in recent years, with some linked to rare cancers.
Purpose of the Study:
- To provide a historical overview of human polyomaviruses.
- To examine the evolution of JCV-induced PML across different time periods.
- To synthesize current knowledge and identify future research directions regarding JCV pathogenesis.
Main Methods:
- Literature review and historical analysis of polyomavirus discoveries.
- Examination of epidemiological data and clinical case studies of PML.
- Synthesis of virological, immunological, and pathological findings related to JCV.
Main Results:
- JCV and BKV are endemic in the human population, typically causing asymptomatic infections.
- The discovery of numerous novel human polyomaviruses has expanded our understanding of this viral family.
- JCV is the causative agent of PML, a severe neurological disease, particularly in immunocompromised individuals.
Conclusions:
- Understanding the transition of JCV from a mostly harmless endemic virus to a cause of lethal disease is crucial.
- Further research is needed to elucidate the complex biology of JCV and its association with PML and cancer.
- Continued surveillance and research into human polyomaviruses are essential for public health.
