Traffic of JC virus from sites of initial infection to the brain: the path to progressive multifocal leukoencephalopathy.
Progressive multifocal leukoencephalopathy (PML) is a demyelinating disorder of the human brain caused by infection with the human polyomavirus, JC. Up to 80% of humans express serum antibodies to JC virus (JCV), yet considerably fewer people develop PML-predominantly those under immunosuppressive conditions. Recent research showed JCV infection in multiple tissues throughout the body, suggesting sites for viral latency. These observations allow the proposal of pathways that JCV may use from sites of initial infection to the brain. Results from investigations into cell-surface receptors, intracellular DNA-binding proteins, and variant viral regulatory regions also suggest mechanisms that may regulate cellular susceptibility to JCV infection. Together, these data elucidate how JCV may establish infection in various cell types, persist latently or become reactivated, and ultimately reach the brain to cause PML.
Sabath
Bruce F
BF
Laboratory of Molecular Medicine and Neuroscience, National Institute of Neurological Disorders and Stroke/NIH, 36 Convent Drive, Bldg. 36, Rm. 5W21, Bethesda, MD 20892, USA.
Major
Eugene O
EO
D001921:Brain / Q000473:pathology / Q000821:virology*; D006801:Humans; D007577:JC Virus / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology; D007968:Leukoencephalopathy, Progressive Multifocal / Q000473:pathology* / Q000821:virology*; D027601:Polyomavirus Infections / Q000473:pathology / Q000821:virology; D014412:Tumor Virus Infections / Q000473:pathology / Q000821:virology; D014775:Virus Activation; D014779:Virus Replication