JCPyV infection occurs possibly either through respiratory route or ingestion. It infects the stromal cells or immune cells of the respiratory tract. Through lymphocyte, the virus goes to bone marrow and kidney and persists there for life. When the immune system of the host gets suppressed, virus comes out from the bone marrow, crosses the blood–brain barrier and enters brain. Inside the brain, it infects the oligodendrocytes, the cell that is responsible for myelin production in the white matter of the human brain. The virus causes lytic infection of the oligodendrocytes and causes progressive multifocal encephalopathy in immunosuppressed hosts.
Almost all progressive multifocal leukoencephalopathy (PML) cases are positive for JCPyV antibody. PML occurs in various types of immunosuppressive conditions, but is the most common amongst AIDS patients. Near 80% of PML cases are AIDS patients, making PML as one of the AIDS defining illnesses in 1–3% HIV infected individuals. The disease is also seen in HIV patients with immune reconstitution inflammatory syndrome (IRIS) due to influx of latently infected immune cells into the brain.
The use of therapeutic monoclonal antibodies, natalizumab, efalizumab and rituximab can induce the immune defects which can trigger the development of PML in those patients.
Clinically PML manifests with progressive focal neurological deficit of motor, cognitive and visual functions. Motor deficit usually manifests as ataxia with difficulties to walk, and talk. Cognitive dysfunction is as of the subcortical dementia.
Laboratory confirmation of PML is done by detection of JCPyV in CSF samples. Estimation of viral load helps as prognostic indicator. Low viral load has been shown with long-term survival of PML patients.
Nucleoside analog (cytarabine arabinoside) has been used in JCPyV diseases which acts by blocking the replication of JCPyV. CMX001, an analog of cidofovir, has been reported to reduce the JCPyV viral load in CSF.
