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[Virological, epidemiological and pathogenic aspects of human polyomaviruses].

UNLABELLED: VIROLOGICAL ASPECTS: Human polyomaviruses (BK virus and JC virus), together with simian polyomaviruses (SV40 virus) share 75% of genomic homology. Their in vivo and in vitro genomes vary. Molecular analyses have identified several genotypes, some of which appear related to the development of viral diseases. Genomic modifications of the regulation area might provide the BKv with a pathogenic aspect thus enhancing the induction of tubulo-interstitial nephropathies in renal transplant recipients. EPIDEMIOLOGY: Human polyomaviruses are ubiquitous and exhibit a sero-prevalence of 60 to…

Progressive multifocal leucoencephalopathy after autologous bone marrow transplantation: a treatment option.

A patient with multiple myeloma was treated with high-dose chemotherapy followed by two autologous bone marrow transplantations (ABMTs). Nine months after the second ABMT the patient complained of severe left hemiparesis, paraesthesias, left homonymous visual field defects and gait ataxia. She was diagnosed with progressive multifocal leucoencephalopathy (PML) confirmed by detection of JC virus (JCV) DNA and prescribed cidofovir every other week and mirtazapine daily. Her symptoms and signs remained stable and after 6 months the JCV DNA was undetectable in the cerebrospinal fluid. Repeated MRI…

Human immunodeficiency virus Tat transactivation: induction of a tissue-specific enhancer in a nonpermissive cell line.

The enhancer of the human neurotropic papovavirus JC virus (JCV) restricts viral transcription to glial cells. We utilized the tissue specificity of the JCV enhancer as a tool to investigate the function of human immunodeficiency virus (HIV) Tat in transcriptional activation. The reporter plasmid pJCTAR-CAT was constructed by inserting the HIV type 1 Tat-responsive element, TAR, between the JCV promoter and the chloramphenicol acetyltransferase (CAT) gene. Cotransfection of pJCTAR-CAT and pSV-Tat, an expression vector for Tat, resulted in a 50-fold increase in JCV promoter activity in cells no…

A Case Control Study Reveals that Polyomaviruria Is Significantly Associated with Interstitial Cystitis and Vesical Ulceration.

OBJECTIVES: To investigate whether polyomaviruses contribute to interstitial cystitis pathogenesis. SUBJECTS AND METHODS: A prospective study was performed with 50 interstitial cystitis cases compared with 50 age-matched, disease-free controls for the frequency of polyomaviruria. Associations between polyomaviruria and disease characteristics were analysed in cases. Polyomavirus in urine and bladder tissue was detected with species (JC virus vs. BK virus) specific, real-time PCR. RESULTS: Case patients were reflective of interstitial cystitis epidemiology with age range from 26-88 years (med…

The human JC polyomavirus (JCPyV): virological background and clinical implications.

JC polyomavirus (JCPyV) was the first of now 12 PyVs detected in humans, when in 1964, PyV particles were revealed by electron microscopy in progressive multifocal leukoencephalopathy (PML) tissues. JCPyV infection is common in 35-70% of the general population, and the virus thereafter persists in the renourinary tract. One third of healthy adults asymptomatically shed JCPyV at approximately 50,000 copies/mL urine. PML is rare having an incidence of <0.3 per 100,000 person years in the general population. This increased to 2.4 per 1000 person years in HIV-AIDS patients without combination anti

JCPyV miR-J1-5p в Урине от Натализумаб-Treated Multical Sclerosis Пациенты.

Использование Natalizumab в мультиклерозе (MS) может привести к возобновлению полиомавируса JC (JCPyV); это может привести к развитию прогрессивной многофукальной лейкоэнцефалопатии (PML), редкой и обычно смертельной болезни. Инфекция JCPyV широко распространена среди населения мира, однако обнаружение антиорганов, противодействующих JCPyV, не является достаточным для выявления инфекции JCPyV, поскольку PML может развиваться даже у пациентов с отрицательной серологией JCPyV. Более глубокое понимание биологии JCPyV могло бы позволить лучше понять инфекцию JCPyV и реактивировать, что, возможно,

Quantitative real-time PCR assay for detection of human polyomavirus infection.

The human polyomaviruses BK (BKV) and JC (JCV) affect immunosuppressed patients and are associated with urogenital tract (BKV) and CNS disorders (JCV) and in humans, the pathogenic role of the rhesus monkey virus, Simian virus 40 (SV40), is uncertain. These three viruses have somewhat overlapping tissue pathogenicity and detection of all three polyomaviruses is desirable. A broadly targeted, simple, single tube real-time degenerated quantitative PCR (QPCR) technique for detection of JCV, BKV and SV40 DNA was developed. To avoid false positive results, due to contamination with commonly used SV

BKV-DNA and JCV-DNA co-quantification assay to evaluate viral load in urine and serum.

Infections from human polyomaviruses BK and JC (BKV and JCV) occur independently, but concomitant infections and the simultaneous persistence of both viruses have been observed in renal transplant recipients. Several studies have disclosed a correlation between BKV and interstitial nephritis in renal transplant recipients, and an association between JCV and some cases of nephropathy has recently been hypothesized. This article describes the development of a semiquantitative-nested polymerase chain reaction (PCR) assay to simultaneously detect BKV and JCV viral load in urine and serum. The firs

[A case of treatment-related leukoencephalopathy during combination therapy with daratumumab, lenalidomide, and low-dose dexamethasone for multiple myeloma].

A 75-year-old woman with multiple myeloma was admitted due to an acute disturbance of consciousness and aphasia two months after administrat … reported, but, in this case, leukoencephalopathy associated with daratumumab was suspected because JC virus DNA was not detected in her cerebrospinal fluid.

Detectable cerebrospinal fluid JCV DNA in late-presenting HIV-positive patients: beyond progressive multifocal leukoencephalopathy?

In the absence of effective prophylaxis and treatment, therapeutic options in HIV-positive patients with progressive multifocal leukoencephalopathy (PML) are limited to antiretroviral therapy: nevertheless, outcome is poor. We conducted a retrospective study (2009-2015) describing the outcome of 25 HIV-positive patients with detectable cerebrospinal fluid JC virus DNA: 14 had a probable PML while the others had evidence of other inflammatory central nervous system (CNS) affecting disorders. In the former group, 6-month mortality was 45.5% vs 21.4 in the latter one: survival was higher than pre…

Ингибирование инфекции JCPyV при помощи целевой редакции вирусного генома с использованием CRISPR/Cas9.

Прогрессивная многофукальная лейкоэнцефалопатия (ПМЛ) — изнурительная болезнь, вызванная инфекцией олигодендроцитов полиомавирусом JC (JCPyV). В настоящее время антивирусная терапия против инфекции JCPyV отсутствует. Система белка 9 (Cas9) (CRISPR/Cas9) представляет собой инструмент редактирования генома, позволяющий вводить в ДНК с двойной блокировкой определенные последовательности переломы. Здесь мы показываем, что система CRISPR/Cas9 может ограничивать жизненный цикл JCPyV в культурных клетках. Мы использовали CRISPR/Cas9 для прицела на область некодового контроля и позднюю открытую рамку

Количественная оценка полиомавируса человека JC в мозговых тканях и цереброспинной жидкости пациентов с прогрессивной многофукальной лейкоэнцефалопатией с помощью конкурентоспособной ПЦР.

Активация полиомавирусной инфекции человека JC (JCV) является причиной заболевания центральной нервной системы (CNS) прогрессивной многофукальной лейкоэнцефалопатии (PML). Предыдущие исследования с неконтролируемыми системами количественной оценки показали, что вирусная нагрузка в CNS соотносится с состоянием болезни и может отражать терапевтические последствия. Поэтому цель этого исследования заключалась в разработке конкурентной системы со стандартными методами ПЦР, которые позволяли бы быстро обнаруживать подтипы JCV, одновременно дифференцировать два полиомавируса человека JCV и BKV, а так

Polymerase chain reaction on cerebrospinal fluid for diagnosis of virus-associated opportunistic diseases of the central nervous system in HIV-infected patients.

OBJECTIVE: To assess the diagnostic reliability of polymerase chain reaction (PCR) on cerebrospinal fluid (CSF) for virus-associated opportunistic diseases of the central nervous system (CNS) in HIV-infected patients. DESIGN: CSF samples from 500 patients with HIV infection and CNS symptoms were examined by PCR. In 219 patients the PCR results were compared with CNS histological findings. METHODS: Nested PCR for detection of herpes simplex virus (HSV) type 1 or 2, varicella zoster virus (VZV), cytomegalovirus (CMV), Epstein-Barr virus (EBV), human herpesvirus 6 (HHV-6), and JC virus (JCV) DN…

Regulation of Polyomavirus Transcription by Viral and Cellular Factors.

Polyomavirus infection is widespread in the human population. This family of viruses normally maintains latent infection within the host cell but can cause a range of human pathologies, especially in immunocompromised individuals. Among several known pathogenic human polyomaviruses, JC polyomavirus (JCPyV) has the potential to cause the demyelinating disease progressive multifocal leukoencephalopathy (PML); BK polyomavirus (BKPyV) can cause nephropathy in kidney transplant recipients, and Merkel cell polyomavirus (MCPyV) is associated with a highly aggressive form of skin cancer, Merkel cell c

Progressive multifocal leukoencephalopathy in idiopathic CD4+ lymphocytopenia: A case report and review of literature.

Progressive multifocal leukoencephalopathy (PML) is a rare demyelinating disease due to a lytic infection of oligodendrocytes caused by polyoma virus (JC virus) infection. PML usually occurs in a setting of severe immunosuppression and is most commonly associated with human immunodeficiency virus (HIV) infection. Idiopathic CD4+ lymphocytopenia is a very rare cause of PML and only a few cases have been reported in the literature. We present a case of a 45-year-old man who presented with behavioral alteration followed by progressive weakness of right side of the body. Contrast-enhanced magnetic…

"Мой язык": Любопытный случай кровавого сэндвича и реактивации вируса Джона Каннингема в эпоху иммуномодулирующих средств.

Прогрессивная многофукальная лейкоэнцефалопатия (ПМЛ) является редким диагнозом, связанным с высокой смертностью в различных клинических условиях. Вирус John Cunningham (JC) (JCV) был объяснен PML. ОЖЦ, как правило, оказывает воздействие на пациентов с ВИЧ/СПИДом, твердыми органами и гематологическими заболеваниями, а также на пациентов, проходящих курс лечения иммуномодулятивными препаратами (ИМИД), как, например, помалидомид. В настоящее время имеется ограниченное число зарегистрированных случаев заболевания множественной миеломой (ММ), которые разработали ПМЛ, о которых сообщалось в литерат

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… Progressive multifocal leukoencephalopathy and the spectrum of JC virus-related disease. Cortese I, Reich DS, Nath A. Nat Rev Neurol. 2021;17:37–51. doi: 10.1038/s41582-020-00427-y. 3. … Diagnostic and prognostic value of JC virus DNA in plasma in progressive multifocal leukoencephalopathy. Ferretti F, Bestetti A, Yiannoutsos CT, et al. Clin Infect Dis. 2018;67:65–72. doi: 10.1093/cid/ciy030. 5. …

[MRI alterations in immunomodulation].

In this review article, typical imaging findings of diseases elicited by immunomodulatory drugs are presented. Progressive multifocal leucoencephalopathy (PML), a subacute infection due to reactivation of the JC virus, has a typical magnetic resonance imaging (MRI) pattern, which must be considered in the framework of immunomodulatory multiple sclerosis (MS) treatment with natalizumab, fingolimod, rituximab and fumarate and also in lymphoproliferative diseases or other forms of immunosuppression. Restoration of the immune system may result in an overlapping and overwhelming immune response in …

Co-occurrence of two cases of progressive multifocal leukoencephalopathy in a natalizumab "infusion group".

We observed two cases of progressive multifocal leukoencephalopathy (PML) that occurred in the same "infusion group". The group consisted of four patients with relapsing-remitting multiple sclerosis (RRMS) who had been treated with natalizumab (NAT) in the same medical practice for more than four years at the same times and in the same room, raising concerns about viral transmission between members of the infusion group. DNA amplification and sequence comparison of the non-coding control region (NCCR) of JC virus (JCV) present in cerebrospinal fluid (CSF) samples from PML patients #1 and #2 re…

[Rare viral infections during immunosuppressive therapy: a "normal" side effect?].

The use of biologicals in the therapy of rheumatic diseases allows more effective treatment of patients with very active disease. Such regimens, however, can induce a more severe treatment-related immunosuppression and, as a consequence, opportunistic infections that are rarely seen with conventional immunosuppressive therapy appear to occur more frequently. The majority of these opportunistic infections are common viral infections which become latent and only cause severe disease if they are reactivated in a severely immunocompromised host. However, some of the newer biologicals, especially n