The JC virus, like the BK virus for example, belongs to the polyomaviruses, a group of non-enveloped DNA viruses. It occurs worldwide and is transmitted in childhood, at which time it can persist for life. The pathogen is the trigger of progressive multifocal leukoencephalopathy, or PML.
What is JC virus?
JC virus (short name: JCPyV) is a worldwide pathogen of the family Polyomaviridae and the genus Polyomavirus. It is also known as human polyomavirus 2 or JC polyomavirus. Absorbed in childhood, the pathogen usually enters the kidney or central nervous system, and probably leukocytes (white blood cells), where it can persist for life. The JC virus is an opportunistic pathogen, which means that it is reactivated when the body suffers from severe immunosuppression. The JC virus is unenveloped, so it does not carry a surrounding lipid envelope. Thus, it is more stable against environmental influences than enveloped viruses. As a genome, the virus carries dsDNA, making it one of the few double-stranded DNA viruses without a lipid envelope. The naming of the JC virus comes from the initials of the patient John Cunningham, in whom the virus was first discovered in 1971.
Occurrence, distribution, and characteristics
JC virus occurs worldwide. Its infection rate is approximately 85 percent. Once infected with the pathogen, it persists throughout life, primarily in the kidney and central nervous system. The virus is also likely to spread in leukocytes. To all appearances, the infection is probably acquired in childhood. It is highly likely that the pathogen is spread orally. More than 60 percent of all U.S. adults have antibodies to the JC virus by age 12. Up to this point, the infection probably runs without any symptoms. However, if the immune system is severely suppressed, as in the case of AIDS or leukemia, for example, the pathogen can reactivate and then destroy the infected cells, releasing them into the bloodstream. There, the virus subsequently spreads to the oligodendroglial cells of the brain, where it can subsequently destroy them as part of the disease. The JC virus is characterized by the absence of a lipid envelope. This lack of an envelope makes the virus resistant to numerous environmental agents. Thus, it also usually escapes killing by disinfection. Furthermore, the JC virus has double-stranded DNA, making it one of the few non-enveloped viruses, along with the adenoviruses, the human papillomaviruses and the BK virus, to have double-stranded DNA. In total, this genome consists of 5130 base pairs, which are divided into three sections. The first section forms the non-coding part, where the origin of replication is located. The second region is responsible for the small, as well as the large T antigen. The third and last region codes for the different envelope proteins, namely the VP1, VP2, as well as the VP3 pentamer. The fact that the non-coding regions can be rearranged results in different JC virus variants. The genome is surrounded by an icosahedral capsid, a protein envelope that protects the virus. The viruses are approximately 45 nm in diameter. The capsid that envelops the virus is composed of 72 capsomers. Mainly these capsomers consist of the VP1 pentamers, the VP2 or the VP3 pentamers are less present in the capsid.
Diseases and disorders
JC virus is the causative agent of progressive multifocal leukoencephalopathy (PML for short), a disease that primarily affects the central nervous system. The disease occurs acutely and continues to develop, which is why it is called progressive. Since almost everyone carries this virus, the disease can affect anyone, but a weakening of the immune system is a prerequisite for the onset of the disease. The first infection with the pathogen in childhood runs without any symptoms. Patients with a weakness of the T-cells, as is the case with AIDS or leukemia, are most frequently affected. If the viruses are reactivated, they travel from the place where they persist for life, such as the kidneys, brain or even bone marrow, via leukocytes to the central nervous system, where they settle in the white matter and multiply. In the process, they primarily attack the oligodendrocytes.These types of cells form the nerve sheaths that surround the nerve cells to ensure optimal conduction of excitation. The oligodendrocytes are destroyed due to the disease, the nerve cells lose their nerve sheath, they become demarcated. There is also an immigration of inflammatory cells, and the demyelination progresses as a result. The symptomatology that develops varies depending on the location of the event. If the cerebellum is affected, motor symptoms such as a disturbance of movement coordination (ataxia) are most noticeable. Furthermore, PML can affect the speech center. Affected persons accordingly suffer from speech disorders. If the visual or auditory pathways are affected, visual field defects or hearing loss occur. In the later course, learning disorders, dementia and concentration difficulties as well as epileptic seizures may occur. In addition to central nervous system (CNS) deficits, JC viruses have been linked to the development of some brain tumors, particularly in animal studies. It is likely that those affected have an increased risk of developing CNS tumors.
