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The hidden secret of the JC virus: Why does it only cause deadly PML when the immune system is weak?
Human polyomavirus 2 (JC virus), as the name suggests, is a human polyomavirus that was first discovered by ZuRhein and Chou under an electron microscope in 1965. The virus is named after a patient named John Cunningham, who developed progressive multifocal leukitis (PML) after infection with the JC virus. The virus can be deadly in patients with weakened immune systems, particularly in those with AIDS or organ transplant patients receiving immunosuppressant therapy.
The initial site of JC virus infection may be the tonsils and perhaps the intestines, where it may remain dormant. It may also infect the tubular epithelial cells of the kidneys and continue to produce viral particles that are excreted in the urine.
The impact of JC virus on the central nervous system (CNS) has attracted the attention of many scholars. The virus can cross the blood-brain barrier, infect oligodendrocytes and astrocytes, and may enter the central nervous system through the 5-HT2A serotonin receptor. Studies have shown that the JC virus in PML patients almost invariably has different promoter sequences in their brain tissue than in healthy individuals. These differences are believed to promote the adaptive development of the virus in the central nervous system, which in turn leads to the development of PML. .
Certain transcription factors within these early promoter sequences are able to induce specificity and viral proliferation, leading to PML. Among them, the Spi-B factor plays a crucial role in initiating viral replication in certain transgenic mice.
Due to conditions of immunodeficiency or immunosuppression, the JC virus can reactivate. In the brain, the virus triggers lethal PML by destroying oligodendrocytes. It is not clear whether this represents reactivation of JC virus within the CNS or newly activated virus disseminated through the blood or lymphatic system.
A large number of studies have shown that JC virus may be related to colon cancer. JC virus has been detected in many malignant intestinal tumors, but the results of these studies are still controversial.
In addition to PML, recent literature has also found variants of the JC virus to be the cause of other emerging diseases. For example, JC virus can infect the granule cell layer of the cerebellum without affecting the large Purkinje cells, ultimately leading to severe cerebellar atrophy. This syndrome, called JCV granular cell neuropathy (JCV GCN), is characterized by productive and lytic infection caused by JC variants harboring mutations in the VP1 coding region.
JC virus may also be a cause of aseptic meningitis because JC virus is the only virus found in the cerebrospinal fluid of some patients with meningitis.
JC virus is very common in the general population, with 70% to 90% of humans becoming infected during their lifetime, mostly during childhood or adolescence. The virus is found in extremely high concentrations in urban and rural sewage around the world, leading some researchers to suspect that contaminated water is a major route of infection.
Regarding the genetic subtypes of the JC virus, scientists have identified 14 subtypes or genotypes based on specific variations in geographical regions. These subtypes help trace human migration patterns, and regional specific subtypes have been found in different populations, which not only have an impact on the characteristics and outcomes of the disease, but also help track the development of human history.
JC virus reactivation has been associated with a variety of drugs. For example, immunosuppressants can lead to JC virus reactivation and PML, and in some medical treatments, patients receiving these drugs are warned against.
Immunosuppressants should be used with extreme caution in patients infected with JC virus. This is directly related to the PML and death cases that may be caused by the JC virus. Many immunosuppressants such as rituximab and natalizumab have been found to be associated with the formation of PML. This has also prompted the medical community to think about how to effectively manage and prevent JC virus infection.
As the JC virus is studied more deeply, the medical community hopes to better understand the virus's underlying mechanisms and its associations with different diseases. Is it possible to find effective prevention or treatment against this potentially deadly virus in the future?
