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The JC virus or John Cunningham virus (JCV) is a type of human polyomavirus
Polyomavirus

Polyomavirus is the sole genus of viruses within the family Polyomaviridae. Polyomaviruses are DNA virus , small , and icosahedron in shape, and do not have a lipoprotein envelope....
 (formerly known as papovavirus
Papovavirus

A Papovaviridae is a member of the Papovaviridae family of viruses. Papovaviridae includes two genus: papillomavirus and polyomavirus....
) and is genetically similar to BK virus
BK virus

The BK virus is a member of the polyomavirus family. Past infection with the BK virus is widespread, but significant consequences of infection are uncommon, with the exception of the immunodeficiency and the immunosuppression....
 and SV40
SV40

SV40 is an abbreviation for Simian vacuolating virus 40 or Simian virus 40, a polyomavirus that is found in both monkeys and humans....
. It was discovered in 1971 and named after the two initials of a patient with progressive multifocal leukoencephalopathy
Progressive multifocal leukoencephalopathy

Progressive multifocal leukoencephalopathy , also known as progressive multifocal leukoencephalitis, is a rare and usually fatal virus disease that is characterized by progressive damage or inflammation of the white matter of the brain at multiple locations ....
 (PML). The virus causes PML and other diseases only in cases of immunodeficiency
Immunodeficiency

Immunodeficiency is a state in which the immune system's ability to fight infectious disease is compromised or entirely absent. Most cases of immunodeficiency are acquired but some people are born with defects in the immune system, or primary immunodeficiency....
, as in AIDS
AIDS

Acquired immune deficiency syndrome or acquired immunodeficiency syndrome is a disease of the human immune system caused by the HIV ....
 or during treatment with drugs intended to induce a state of immunosuppression
Immunosuppression

Immunosuppression involves an act that reduces the activation or efficacy of the immune system. Some portions of the immune system itself have immuno-suppressive effects on other parts of the immune system, and immunosuppression may occur as an adverse reaction to treatment of other conditions....
 (e.g. organ transplant
Organ transplant

Organ transplant is the moving of an organ from one body to another , for the purpose of replacing the recipient's damaged or failing organ with a working one from the donor site....
 patients).

virus is very common in the general population, infecting 70 to 90 percent of humans; most people acquire JCV in childhood or adolescence .






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Encyclopedia


The JC virus or John Cunningham virus (JCV) is a type of human polyomavirus
Polyomavirus

Polyomavirus is the sole genus of viruses within the family Polyomaviridae. Polyomaviruses are DNA virus , small , and icosahedron in shape, and do not have a lipoprotein envelope....
 (formerly known as papovavirus
Papovavirus

A Papovaviridae is a member of the Papovaviridae family of viruses. Papovaviridae includes two genus: papillomavirus and polyomavirus....
) and is genetically similar to BK virus
BK virus

The BK virus is a member of the polyomavirus family. Past infection with the BK virus is widespread, but significant consequences of infection are uncommon, with the exception of the immunodeficiency and the immunosuppression....
 and SV40
SV40

SV40 is an abbreviation for Simian vacuolating virus 40 or Simian virus 40, a polyomavirus that is found in both monkeys and humans....
. It was discovered in 1971 and named after the two initials of a patient with progressive multifocal leukoencephalopathy
Progressive multifocal leukoencephalopathy

Progressive multifocal leukoencephalopathy , also known as progressive multifocal leukoencephalitis, is a rare and usually fatal virus disease that is characterized by progressive damage or inflammation of the white matter of the brain at multiple locations ....
 (PML). The virus causes PML and other diseases only in cases of immunodeficiency
Immunodeficiency

Immunodeficiency is a state in which the immune system's ability to fight infectious disease is compromised or entirely absent. Most cases of immunodeficiency are acquired but some people are born with defects in the immune system, or primary immunodeficiency....
, as in AIDS
AIDS

Acquired immune deficiency syndrome or acquired immunodeficiency syndrome is a disease of the human immune system caused by the HIV ....
 or during treatment with drugs intended to induce a state of immunosuppression
Immunosuppression

Immunosuppression involves an act that reduces the activation or efficacy of the immune system. Some portions of the immune system itself have immuno-suppressive effects on other parts of the immune system, and immunosuppression may occur as an adverse reaction to treatment of other conditions....
 (e.g. organ transplant
Organ transplant

Organ transplant is the moving of an organ from one body to another , for the purpose of replacing the recipient's damaged or failing organ with a working one from the donor site....
 patients).

Epidemiology

The virus is very common in the general population, infecting 70 to 90 percent of humans; most people acquire JCV in childhood or adolescence . It is found in high concentrations in urban sewage worldwide, leading some researchers to suspect contaminated water as a typical route of infection .

Minor genetic variations are found consistently in different geographic areas; thus, genetic analysis of JC virus samples has been useful in tracing the history of human migration .

Infection and pathogenesis

The initial site of infection may be the tonsil
Tonsil

Palatine tonsils, occasionally called the faucial tonsils, are the tonsils that can be seen on the left and right sides at the back of the throat....
s, or possibly the gastrointestinal tract
Gastrointestinal tract

The digestive tract is the system of Organ s within multicellular animals that takes in food, digestion it to extract energy and nutrients, and expels the remaining waste....
. The virus then remains latent in the gastrointestinal tract and can also infect the tubular epithelial
Epithelium

In biology and medicine, epithelium is a Biological tissue composed of cell s that line the cavities and surfaces of structures throughout the body....
 cells in the kidney
Kidney

The kidneys are Organ that have numerous biological roles. Their primary role is to maintain the homeostasis balance of bodily fluids by filtering and secreting Metabolomics#Metabolitess and minerals from the blood and excreting them, along with water , as urine....
s, where it continues to reproduce, shedding virus
Viral shedding

Viral shedding refers to the successful reproduction, expulsion, and host-cell infection caused by virus progeny. Once replication has been completed and the host cell is exhausted of all resources in making viral progeny, the viruses may begin to leave the cell by several methods....
 particles in the urine.

JCV can cross the blood-brain barrier
Blood-brain barrier

The blood-brain barrier is a metabolic or cellular structure in the central nervous system that restricts the passage of various chemical substances and microscopic objects between the bloodstream and the neural tissue itself, while still allowing the passage of substances essential to metabolism function ....
 into the central nervous system
Central nervous system

The central nervous system is the part of the nervous system that functions to coordinate the activity of all parts of the bodies of multicellular organisms....
, where it infects oligodendrocyte
Oligodendrocyte

Oligodendrocytes , or oligodendroglia , are a variety of neuroglia. Their main function is the insulation of the axons exclusively in the central nervous system of the higher vertebrates, a function performed by Schwann cells in the peripheral nervous system....
s and astrocyte
Astrocyte

Astrocytes are characteristic star-shaped neuroglia cell in the brain and spinal cord. They perform many functions, including biochemical support of endothelial cells which form the blood-brain barrier, the provision of nutrients to the nervous tissue, and a principal role in the repair and scarring process of the brain and spinal cord fol...
s, possibly through the 5-HT2A
5-HT receptor

In the field of neurochemistry, 5-HT receptors are receptor for the neurotransmitter and Periphery signal mediator serotonin, also known as 5-hydroxytryptamine or 5-HT....
 serotonin
Serotonin

Serotonin is a monoamine neurotransmitter synthesized in serotonergic neurons in the central nervous system and enterochromaffin cells in the gastrointestinal tract of animals including humans....
 receptor
Receptor (biochemistry)

In biochemistry, a receptor is a protein molecule, embedded in either the plasma membrane or cytoplasm of a cell, to which a mobile signaling molecule may attach....
. JC viral DNA can be detected in both non-PML affected as well as PML-affected (see below) brain tissue.

Immunodeficiency or immunosuppression allows JCV to reactivate. In the brain
Brain

The brain is the center of the nervous system in all vertebrate, and most invertebrate, animals. Some primitive animals such as cnidarian and echinoderm have a decentralized nervous system without a brain, while sponges lack any nervous system at all....
 it causes the usually fatal progressive multifocal leukoencephalopathy
Progressive multifocal leukoencephalopathy

Progressive multifocal leukoencephalopathy , also known as progressive multifocal leukoencephalitis, is a rare and usually fatal virus disease that is characterized by progressive damage or inflammation of the white matter of the brain at multiple locations ....
, or PML, by destroying oligodendrocytes. Whether this represents the reactivation of JCV within the CNS or seeding of newly reactivated JCV via blood or lymphatics is unknown. Several studies since 2000 have suggested that the virus is also linked to colorectal cancer
Colorectal cancer

Colorectal cancer, also called colon cancer or large bowel cancer, includes cancerous growths in the colon , rectum and Vermiform appendix....
, as JCV has been found in malignant colon
Colon (anatomy)

The colon is the last portion of the digestive system in most vertebrates; it extracts water and salt from feces before they are defecation from the body....
 tumors, but these findings are still controversial.

Drug Interactions


The boxed warning for the drug rituximab
Rituximab

Rituximab, sold under the trade names Rituxan and MabThera, is a Chimera monoclonal antibody against the protein CD20. Rituximab is used in the treatment of B cell non-Hodgkin's lymphoma, B-cell leukemias, and some autoimmune disorders....
 (Rituxan, co-marketed by Genentech BioOncology and Biogen Idec) includes that JC virus infection resulting in progressive multifocal leukoencephalopathy
Progressive multifocal leukoencephalopathy

Progressive multifocal leukoencephalopathy , also known as progressive multifocal leukoencephalitis, is a rare and usually fatal virus disease that is characterized by progressive damage or inflammation of the white matter of the brain at multiple locations ....
 and death has been reported in patients treated with the drug .

The boxed warning for the drug natalizumab
Natalizumab

Natalizumab is a humanized antibody monoclonal antibody against the cellular adhesion molecule integrin. Natalizumab is used in the treatment of multiple sclerosis and Crohn's disease....
 (Tysabri, marketed by Elan and developed by Biogen Idec) includes that JC virus resulting in progressive multifocal leukoencephalopathy developed in three patients who received natalizumab in clinical trials.

The boxed warning was added Feb. 19, 2009 for the drug efalizumab
Efalizumab

Efalizumab is a medication used to treat psoriasis. As its Nomenclature of monoclonal antibodies, it is a recombinant humanized monoclonal antibody that binds to CD11a and acts as an immunosuppressant....
 (Raptiva, marketed in the U.S. by Genentech, and marketed in Europe by Swiss drugmaker Merck Serono) includes that JC virus resulting in progressive multifocal leukoencephalopathy developed in three patients who received natalizumab in clinical trials.

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