Contributions
Abstract: 155
Type: Oral
The polyomavirus JC (JCV) is the etiologic agent of progressive multifocal leukoencephalopathy (PML), a demyelinating disease of the central nervous system (CNS). PML occurs in the setting of profound immunossuppresion, but has also been associated with a growing number of immunomodulatory medications used for the treatment of auto-immune diseases, including multiple sclerosis (MS) and Crohn"s disease. After immune recovery, triggered by antiretroviral medications in HIV-infected patients or discontinuation of chemical immunosuppression in HIV-seronegative individuals, PML can be associated with an intense inflammation, called immune reconstitution inflammatory syndrome (IRIS). For more than 30 years, JCV was thought to exclusively infect oligodendrocytes and astrocytes in the white matter of the brain of immunosuppressed individuals. We now recognize that JCV-infected glial cells are frequently located at the gray-white matter junction or exclusively within the gray matter causing demyelination in the cortex. Mutations in JCV can trigger a change in tropism leading to involvement of other cell types, such as neurons and meningeal cells causing clinically distinct entities: JC virus granule cell neuronopathy (JCV GCN), JC virus encephalopathy (JCVE) and JC virus meningitis (JCVM). Furthermore, JCV can also infect hippocampal neurons. These new features of JCV infection explain a very high prevalence of seizures in PML, which can be used as a model of acquired epilepsy. They also provide challenges for clinicians taking care of affected patients and investigators studying the biology of this polyomavirus, its pathogenesis, and tropism.
Disclosure: Dr. Koralnik is funded in part by NIH grant R01NS 047029 and NS 074995, and grants from Biogen and the CURE foundation. He has served on scientific advisory boards for Hoffmann La Roche, GlaxoSmithKline, Merck Serono, and MedImmune; received consulting fees from Bristol Myers Squibb, Ono Pharmaceuticals, Merck Serono, Hoffmann La Roche, GlaxoSmithKline, Perseid Therapeutics, Vertex Pharmaceuticals, and Johnson & Johnson; is an Associate Editor for the Annals of Neurology; and receives royalties from UpToDate for topics on the management of HIV and CNS mass lesions and on PML.
Abstract: 155
Type: Oral
The polyomavirus JC (JCV) is the etiologic agent of progressive multifocal leukoencephalopathy (PML), a demyelinating disease of the central nervous system (CNS). PML occurs in the setting of profound immunossuppresion, but has also been associated with a growing number of immunomodulatory medications used for the treatment of auto-immune diseases, including multiple sclerosis (MS) and Crohn"s disease. After immune recovery, triggered by antiretroviral medications in HIV-infected patients or discontinuation of chemical immunosuppression in HIV-seronegative individuals, PML can be associated with an intense inflammation, called immune reconstitution inflammatory syndrome (IRIS). For more than 30 years, JCV was thought to exclusively infect oligodendrocytes and astrocytes in the white matter of the brain of immunosuppressed individuals. We now recognize that JCV-infected glial cells are frequently located at the gray-white matter junction or exclusively within the gray matter causing demyelination in the cortex. Mutations in JCV can trigger a change in tropism leading to involvement of other cell types, such as neurons and meningeal cells causing clinically distinct entities: JC virus granule cell neuronopathy (JCV GCN), JC virus encephalopathy (JCVE) and JC virus meningitis (JCVM). Furthermore, JCV can also infect hippocampal neurons. These new features of JCV infection explain a very high prevalence of seizures in PML, which can be used as a model of acquired epilepsy. They also provide challenges for clinicians taking care of affected patients and investigators studying the biology of this polyomavirus, its pathogenesis, and tropism.
Disclosure: Dr. Koralnik is funded in part by NIH grant R01NS 047029 and NS 074995, and grants from Biogen and the CURE foundation. He has served on scientific advisory boards for Hoffmann La Roche, GlaxoSmithKline, Merck Serono, and MedImmune; received consulting fees from Bristol Myers Squibb, Ono Pharmaceuticals, Merck Serono, Hoffmann La Roche, GlaxoSmithKline, Perseid Therapeutics, Vertex Pharmaceuticals, and Johnson & Johnson; is an Associate Editor for the Annals of Neurology; and receives royalties from UpToDate for topics on the management of HIV and CNS mass lesions and on PML.