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Overview of the cellular immunity against JC virus in progressive multifocal leukoencephalopathy.

The human polyomavirus JC (JCV) infects most healthy adults without causing any disease. In the setting of severe deficit of cell-mediated immunity, such as in acquired immunodeficiency syndrome (AIDS), malignancies or in organ transplant recipients, JCV can reactivate and cause progressive multifocal leukoencephalopathy (PML), a deadly demyelinating disease of the central nervous system. The humoral immune response, measured by the presence of virus-specific immunoglobulin G (IgG) in the blood or by intrathecal synthesis of IgG in the cerebrospinal fluid (CSF), is unable to contain the progre

Вирусные цитотоксичные Т лимфоциты у людей с прогрессивной многофукальной лейкоэнцефалопатией.

Прогрессивная многофукальная лейкоэнцефалопатия (PML) — демиелионирующая болезнь центральной нервной системы, вызванная возобновлением полиомавируса JC (JCV) в условиях иммуносуппрессии. Природа иммунной реакции, которая содержит воспроизведение этого вируса, неизвестна. Мы изучили клеточную реакцию JCV у пациентов с PML и контрольными субъектами. В случае четырех инфицированных вирусом иммунодефицита человека (ВИЧ) пациентов, выживших в результате PML, и одного больного ВИЧ-инфекционным заболеванием, недавно диагностировавшего PML лизинговые аутометрические линии клеток B-лимфоболоидных клето

Progressive multifocal leukoencephalopathy: JC virus induced demyelination in the immune compromised host.

Progressive multifocal leukoencephalopathy (PML) is a fatal demyelinating disease of the central nervous system that predominantly affects immunocompromised individuals. The etiologic agent, JCV, is a widespread polyomavirus with a very specific target, the myelin-producing oligodendrocytes of the brain. During periods of immune suppression, the virus can be reactivated from lymphoid tissues and kidney, causing targeted myelin destruction and corresponding neurological deficits. The incidence of PML has increased in recent years, due in large part to the advent of AIDS and the growing number o

JC virus DNA load in patients with and without progressive multifocal leukoencephalopathy.

OBJECTIVE: To determine the clinical value of JC virus (JCV) detection in various anatomic compartments for the diagnosis of progressive multifocal leukoencephalopathy (PML). METHODS: CSF, peripheral blood mononuclear cells (PBMC), plasma, and urine samples were evaluated from HIV-infected and uninfected individuals. JCV DNA was detected by PCR and was quantified using a competitive PCR ELISA. RESULTS: JCV DNA was detected in one-third of the urine samples, regardless of HIV serostatus or clinical evidence of PML. JCV DNA was detected in five of eight PBMC and three of seven plasma samples o…

Isolation of a possible archetypal JC virus DNA sequence from nonimmunocompromised individuals.

We molecularly cloned JC polyomavirus DNAs from urine samples of eight nonimmunosuppressed patients and two healthy individuals. The cloned viral DNAs all contained an archetypal regulatory sequence from which various regulatory sequences of JC polyomavirus isolates derived from patients with progressive multifocal leukoencephalopathy could have evolved by deletion and amplification.

Presumed Bilateral Retinitis Associated with JC Virus in a Patient with HIV AIDS.

PURPOSE: To report the clinical characteristics of JC virus (JCV) retinitis. METHODS: A retrospective case report. RESULTS: A 29-year-old male patient, diagnosed with HIV at AIDS stage, had brain lesions compatible with progressive multifocal leukoencephalopathy. Fundus examination showed areas of retinal atrophy and changes in the pigment epithelium. A similar worsening of the retinal and brain lesions was observed, despite several treatments. The vitreous sample analyzed using Next Generation Sequencing analysis was positive for JCV. No other pathogens were identified. The retinal lesions …

Predictive value of JC virus PCR in cerebrospinal fluid in the diagnosis of PML.

OBJECTIVE: To assess the predictive value of JC virus (JCV) PCR in cerebrospinal fluid (CSF) in the diagnosis of progressive multifocal leukoencephalopathy (PML). METHODS: We conducted a retrospective database query to identify patients with positive CSF JCV PCR. Clinical features, final diagnosis and quantitative PCR results were obtained. RESULTS: A positive CSF JCV PCR had a PPV of 10.4% for the diagnosis of PML. A weakly positive PCR had a PPV of 1.6%, whereas a moderately to highly positive PCR had a PPV of 92.3%. A PPV of 0.0% was observed in immunocompetent patients and in patients wi…

CD34+ progenitor cells mobilized by natalizumab are not a relevant reservoir for JC virus.

BACKGROUND: Progressive multifocal leukoencephalopathy (PML) is associated with natalizumab treatment in patients with multiple sclerosis (MS). It has been hypothesized that natalizumab mobilizes JC virus (JCV)-infected haematopoietic progenitor cells mediating viraemia and subsequently this disease. OBJECTIVE: The objective of this study was to investigate peripheral haematopoietic progenitor cells for evidence of JCV DNA in MS patients treated with natalizumab. METHODS: We assessed JCV and cytomegalovirus (CMV) DNA in magnetically separated CD34+ haematopoietic progenitor cells, peripheral…

Induction of undifferentiated brain tumors in rats by a human polyomavirus (JC virus).

Newborn SD rats were inoculated intracranially with JC virus (Tokyo-1), a human polyomavirus, isolated from the autopsied brain of a patient with progressive multifocal leukoencephalopathy. Twenty-one to 61 weeks later, 20 of 27 rats developed tumors in the cerebrum, but not in the cerebellum. The undifferentiated neuroectodermal nature of the tumors was histologically, immunohistochemically and ultrastructurally confirmed.

A fatal case of JC virus meningitis presenting with hydrocephalus in a human immunodeficiency virus-seronegative patient.

JC virus (JCV) is the etiologic agent of progressive multifocal leukoencephalopathy, JCV granule cell neuronopathy, and JCV encephalopathy. Whether JCV can also cause meningitis has not yet been demonstrated. We report a case of aseptic meningitis resulting in symptomatic hydrocephalus in a human immunodeficiency virus-seronegative patient. Brain imaging showed enlargement of ventricles but no parenchymal lesion. She had a very high JC viral load in the cerebrospinal fluid (CSF) and developed progressive cognitive dysfunction despite ventricular drainage. She was diagnosed with pancytopenia an…

Development of primary central nervous system lymphoma associated with human immunodeficiency virus and JC virus infection.

We report here a case of a 37-year-old man with human immunodeficiency virus (HIV) infection followed by JC virus (JCV) infection and primary central nervous system lymphoma (PCNSL). The patient had been infected with HIV type 1 due to blood products for hemophilia A during infancy. He had progression of nervous symptoms and was diagnosed with progressive multifocal leukoencephalopathy (PML) clinically at the age of 36, when his CD4-positive lymphocyte counts ranged between 350 and 450/μl. Oral mefloquine, intravenous methylprednisolone pulse therapy, and intravenous immunoglobulin were not ef…

Molecular characterization of JC virus in progressive multifocal leukoencephalopathy cases from India.

Progressive Multifocal Leukoencephalopathy (PML) is a rare, often fatal demyelinating disease of the central nervous system caused by reacti … gan transplant recipients and those with autoimmune disorders, further emphasizes the need to study JC virus diversity in the Indian context. This study aimed to characterize the genetic diversity of JCV in India by sequencing the VP1 and non-coding control region (NCCR) from cerebrospinal fluid (n=30) of confirmed PML cases using Sanger sequencing. VP1 se …

A human-derived 3D brain organoid model to study JC virus infection.

Progressive multifocal leukoencephalopathy (PML) is a frequent neurological complication in immunosuppressed patients. PML is caused by the JC virus (JCV), a neurotropic DNA polyomavirus that infects oligodendrocytes and astrocytes, causing inflammation and demyelination which lead to neurological dysfunction. The pathogenesis of PML is poorly understood due to the lack of in vitro or animal models to study mechanisms of disease as the virus most efficiently infects only human cells. We developed a human-derived brain organotypic system (also called brain organoid) to model JCV infection. The …

Ocrelizumab after natalizumab in JC-virus positive relapsing remitting multiple sclerosis patients.

Ocrelizumab is often used as an alternative therapy in natalizumab-treated MS patients at risk for progressive multifocal leukoencephalopathy (PML). Our objective was to assess efficacy and safety of JC-virus positive patients switching (either directly or indirectly) from natalizumab to ocrelizumab. Forty-two patients were included from an observational cohort (median follow-up 21 months). No evidence of disease activity was found in 83% of direct switchers and 50% of indirect switchers. Two direct switchers were diagnosed with carry-over PML. Our data support a direct switch for adequate dis

High cumulative JC virus seroconversion rate during long-term use of natalizumab.

BACKGROUND AND PURPOSE: John Cunningham virus (JCV) seropositivity is a risk factor for the development of natalizumab-associated progressive multifocal leukoencephalopathy (PML) in multiple sclerosis (MS) patients. When JCV seronegative patients seroconvert, their risk of developing PML increases. Limited longitudinal data exist about the seroconversion rate amongst natalizumab-treated relapsing-remitting MS (RRMS) patients. Our objective was to evaluate the seroconversion rate in a large Dutch cohort of natalizumab-treated RRMS patients. Seroconversion was defined as at least two consecutive

Вирусные нуклеотиды 376-396 имеют решающее значение для белкового выражения VP1 Capsid.

Вирусная инфекция мозга (JCV) может вызывать прогрессирующую многофукальную лейкоэнцефалопатию, гранулевую нейронопатию клеток и энцефалопатию JCV (JCV). JCVCPN, изолированный от мозга пациента с JCVE, является естественным штаммом JCV с 143-базовым удалением пары в агногене. Исследования клеточной культуры JCVCPN показали, что потеря этих нуклеотидов в агногене приводит к поврежденному выражению VP1 и инфекционного вирионного производства. Чтобы лучше понять роль этой последовательности ДНК в репликации JCV, мы создали серию удалёний в агногене на позвоночнике вируса, у которого мутированный

Совпадение в аннотации оригинала
JC virus (JCV) infection of the brain can cause progressive multifocal leukoencephalopathy, JCV granule cell neuronopathy, and JCV encephalopathy (JCVE). JCVCPN, isolated from the brain of a patient with JCVE, is a naturally occurring strain of JCV with a 143-base pair deletion in the agnogene. Cell culture studies of JCVCPN have shown that the loss of these…

[New approach for JC virus detection and its application for PML diagnosis].

Progressive multifocal leukoencephalopathy (PML) is a rare but fatal demyelinating disease of the central nervous system (CNS) caused by JC virus (JCV). The current diagnostic standard for PML is real-time PCR testing of extracted DNA for assessing the presence of JCV DNA in cerebrospinal fluid (CSF). However, because of its sensitivity, real-time PCR assay for JCV testing has a risk of false-positive results due to DNA contamination. JCV isolates recovered from the brain or CSF of PML patients contain hypervariable mutations within the non-coding control region (NCCR) of the viral genome. In …

JC virus encephalopathy is associated with a novel agnoprotein-deletion JCV variant.

JC virus encephalopathy (JCVE) is a newly described gray matter disease of the brain caused by productive infection of cortical pyramidal neurons. We characterized the full length sequence of JCV isolated from the brain of a JCVE patient, analyzed its distribution in various compartments by PCR, and determined viral gene expression in the brain by immunohistochemistry(IHC). We identified a novel JCV variant, JCV(CPN1), with a unique 143 bp deletion in the Agno gene encoding a truncated 10 amino acid peptide, and harboring an archetype-like regulatory region. This variant lacked one of three nu…

Suppressive effect of PARP-1 inhibitor on JC virus replication in vitro.

The incidence of progressive multifocal leukoencephalopathy (PML) has increased due to the AIDS pandemic, hematological malignancies, and immunosuppressive therapies. Recently, the number of cases of monoclonal antibody-associated PML has increased in patients treated with immunomodulatory drugs such as natalizumab. However, no common consensus regarding PML therapy has been reached in clinical studies. In order to examine the suppression of JC virus (JCV) replication by 3-aminobenzamide (3-AB), a representative PARP-1 inhibitor, a DNA replication assay was carried out using the neuroblastoma …

JC virus granule cell neuronopathy is associated with VP1 C terminus mutants.

The polyomavirus JC (JCV) infects glial cells and causes progressive multifocal leukoencephalopathy (PML). We described a novel JCV-variant with a 10 bp deletion in the C terminus of the VP1 capsid protein, JCV(GCN1). This mutant was associated with lytic infection of cerebellar granule cell neurons and cerebellar atrophy in an human immunodeficiency virus/PML patient. This condition, also observed independently from PML, was named JCV granule cell neuronopathy (JCV GCN). We characterized JCV mutations in cerebrospinal fluid (CSF) of four other JCV GCN patients, and reviewed the literature on