Neuroinfectious Diseases
Philip B. Gorelick, Fernando D. Testai, Graeme J. Hankey, Joanna M. Wardlaw in Hankey's Clinical Neurology, 2020
JC virus infection is ubiquitous and usually acquired in childhood, with approximately 70–85% of adults in the United States possessing antibodies to the virus.1,2 PML was once quite rare, but the HIV pandemic has changed the epidemiology dramatically. PML was seen occasionally in patients with hematologic malignancies,3,4 steroid use,5 or the rare patient of advanced age. It has also been reported in presumably immunocompetent individuals. However, PML is currently considered a disease of the immunocompromised, particularly those with AIDS, and patients receiving cytotoxic chemotherapy or other immunosuppressive agents. More than 50% of all deaths from PML occur in HIV-infected individuals, and it is estimated that 1–4% of patients with HIV will develop PML.6
Laboratory Diagnosis of CNS Viral Infections
Sunit K. Singh, Daniel Růžek in Neuroviral Infections, 2013
JC virus is a neurotropic virus that causes progressive multifocal leukoencephalopathy (PML), which generally occurs after the reactivation of JC virus within the CNS, usually in the setting of immunosuppression. PML was rare prior to the HIV epidemic and is an AIDS-defining illness. More recently, PML has been linked to monoclonal antibody use, in particular natalizumab, in relapsing—remitting multiple sclerosis and inflammatory bowel disease (Linda et al. 2009; Van Assche et al. 2005). In addition to classical PML, JC virus can also cause granular cell neuronopathy and encephalitis (Tan and Koralnik 2010) Immune reconstitution inflammatory syndrome after plasma exchange in individuals with multiple sclerosis treated with natalizumab has also been recently described (Tan et al. 2011).
Cidofovir and Brincidofovir
M. Lindsay Grayson, Sara E. Cosgrove, Suzanne M. Crowe, M. Lindsay Grayson, William Hope, James S. McCarthy, John Mills, Johan W. Mouton, David L. Paterson in Kucers’ The Use of Antibiotics, 2017
Several reports point to the efficacy of CDV for treatment of progressive multifocal leukoencephalopathy (PML), caused by JC polyomavirus, in patients with HIV infection, given at the dosage regimen recommended for the treatment of HCMV retinitis in HIV-infected patients (Taoufik et al., 1998). In a series of 12 AIDS patients, JC viral loads in the cerebrospinal fluid (CSF) correlated with survival time, suggesting that JC viral load in CSF could be considered a prognostic marker for the clinical outcome of PML. CSF JC viral load decreased and then became undetectable in 1 PML patient receiving intravenous CDV treatment, starting 2 months after the onset of PML symptoms. A total of 11 infusions of CDV concomitant with saline prehydration and oral probenecid were given during a period of 4 months. Treatment with CDV was associated with clinical improvement. These results showed that CSF JC viral load may be useful as a prognostic marker and in monitoring the effectiveness of anti-JC virus therapies in PML patients (Taoufik et al., 1998).
JC polyomavirus: a short review of its biology, its association with progressive multifocal leukoencephalopathy, and the diagnostic value of different methods to manifest its activity or presence
Published in Expert Review of Molecular Diagnostics, 2023
Carla Prezioso, Valeria Pietropaolo, Ugo Moens, Marco Ciotti
In 1958, Åstrom and colleagues described a fatal demyelinating condition affecting multiple foci of the subcortical white matter in two patients suffering from chronic lymphocytic leukemia and one with Hodgkin’s lymphoma and named the disease Progressive Multifocal Leukoencephalopathy (PML) [1]. Patients with PML were rare, and the cause of this disease was an enigma. Because of the presence of inclusion bodies in oligodendrocytes, a viral etiology hypothesis was put forward [2,3]. Electron microscopic observations in the 1960s of PML affected brain tissue confirmed the presence of icosahedral shaped virus particles resembling papovavirus in these intranuclear inclusions [4,5]. Several years later, Padgett and colleagues succeeded in isolating this virus and propagating it in primary fetal glial cells. They named the virus J.C. after the initials of the patient [6] and of ethical considerations the patient’s full name should not be used [7]. JC virus is currently classified as a polyomavirus (PyV) belonging to the Polyomaviridae family, genus Betapolyomavirus, species Betapolyomavirus secuhominis. The International Committee on Taxonomy of Viruses proposed to use the binomial nomenclature JC polyomavirus (abbreviated as JCPyV) or betapolyomavirus secuhominis [8].
Perivascular tissue resident memory T cells as therapeutic target in multiple sclerosis
Published in Expert Review of Neurotherapeutics, 2020
Joost Smolders, Nina L. Fransen, Cheng-Chih Hsiao, Jörg Hamann, Inge Huitinga
Since brain CD4+ and CD8+ TRM cells are physiological residents of the normal human PVS [41,42], therapeutic strategies interfering with their functional profile may disrupt physiological functions of these cells. In MS, the importance of physiological T-cell trafficking to the CNS became eminent with the development of PML in natalizumab-treated patients[121]. Therefore, a role of physiological TRM-cell pools in immune surveillance of the CNS can be anticipated. The risks of interfering directly with this surveillance are not known. Although JC virus has been propagated to be retained in an inactive state in the kidneys[122], postmortem human studies also revealed JC virus genetic fragments in brains of 28–68% of asymptomatic cases [123–125]. The latter observations suggests JC virus to latently infect the human CNS, flaring up in the case of PML.
How not to discover a drug - integrins
Published in Expert Opinion on Drug Discovery, 2021
While a promising therapy for both MS and Crohn’s there was a serious safety concern with natalizumab. It was associated with reactivation of JC virus infection leading to Progressive Multifocal Leukoencephalopathy (PML) [140] due to lysis of neurons and permanent destruction of the myelin sheath. In patients that are JC virus positive the incidence of PML is 1% with a 25% mortality rate and 30% of survivors will have severe neurological complications [141]. This was to be a major blow for natalizumab. While it was an effective disease-modifying therapy its safety profile was of concern. Although it was not withdrawn from the market it is only prescribed under a risk evaluation and mitigation strategy (REMS). With the advent of newer disease modifying therapies such as fingolimod and dimethyl fumarate it is no longer a frontline treatment. PML is not unique to natalizumab with a number of other immune suppressants associated with PML however, the incidence is much higher with natalizumab.
Related Knowledge Centers
- Epithelium
- Gastrointestinal Tract
- Immunosuppression
- Progressive Multifocal Leukoencephalopathy
- Polyomaviridae
- Papovaviricetes
- Immunodeficiency
- HIV/AIDS
- Organ Transplantation
- Tonsil