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JC polyomavirus whole genome sequencing at the single molecule level reveals emerging viral populations in Progressive Multifocal Leucoencephalopathy

ABSTRACT: JC polyomavirus whole genome sequencing at the single molecule level reveals emerging viral populations in Progressive Multifocal Leucoencephalopathy

PROVIDER: PRJEB49243 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	ERR7569960.fastq.gz	Fastqsanger.gz
	ERR7569970.fastq.gz	Fastqsanger.gz
	ERR7569980.fastq.gz	Fastqsanger.gz
	ERR7569990.fastq.gz	Fastqsanger.gz
	ERR7569961.fastq.gz	Fastqsanger.gz

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JC polyomavirus whole genome sequencing at the single molecule level reveals emerging viral populations in Progressive Multifocal Leucoencephalopathy

Project description:JC polyomavirus (circular genome) contains two opposite coding regions separated by the regulator non-coding control region (NCCR). NCCR rearrangements and missense mutations in the viral capsid protein VP1 gene differentiate JCV prototype genomes recovered from PML lesions from archetype urine strains. To further investigate the emerging variability of JCV populations in PML, we deep sequenced JCV whole genome recovered from CNS and/or urine samples from HIV- and non HIV-infected PML patients, using single-molecule real-time sequencing (PacBio, Paciﬁc Biosciences). Phylogenetic analysis showed that PML strains distributed among 6 of 7 known genotypes. Whole genome single molecule sequencing provides insight in the genesis of JCV neurotropic populations.

2022-01-12 | E-MTAB-11077 | biostudies-arrayexpress

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Project description:Identification of quasispecies in JC virus genome in patients with progressive multifocal leukoencephalopathy by deep sequencing

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Comprehensive proteomic analysis of JC polyomavirus-infected human astrocytes and their extracellular vesicles

Project description:JC polyomavirus (JCPyV) is the causative agent of progressive multifocal leukoencephalopathy (PML), a devastating demyelinating disease of the central nervous system that results in the widespread formation of lesions across the brain parenchyma. The virus is opportunistic and remains in a benign state in the kidneys and lymphoid organs of more than half of the global human adult population. However, in rare cases of severe or selective immune suppression, JCPyV can establish a lytic infection of glial cells in the brain. While PML has traditionally been characterized as a lytic infection of oligodendrocytes, more recent findings suggest an important role for astrocytes during the initial stages of disease. Because of the exceptional species and tissue specificity of the virus, appropriate models of JCPyV infection in the brain are lacking, thus hampering progress towards the development of novel antiviral strategies and biomarkers of disease activity. Here, using iPSC-derived astrocytes infected with JCPyV and analyzed by LC-MS/MS, we show that the virus strongly influences the cell biology, inducing an unique proteomic signature that sharply contrasts with mock-infected cells.

2023-08-28 | PXD044144 | Pride

Comprehensive proteomic analysis of JC polyomavirus-infected human astrocytes and their extracellular vesicles

Project description:JC polyomavirus (JCPyV) is the causative agent of progressive multifocal leukoencephalopathy (PML), a devastating demyelinating disease of the central nervous system that results in the widespread formation of lesions across the brain parenchyma. The virus is opportunistic and remains in a benign state in the kidneys and lymphoid organs of more than half of the global human adult population. However, in rare cases of severe or selective immune suppression, JCPyV can establish a lytic infection of glial cells in the brain. While PML has traditionally been characterized as a lytic infection of oligodendrocytes, more recent findings suggest an important role for astrocytes during the initial stages of disease. Because of the exceptional species and tissue specificity of the virus, appropriate models of JCPyV infection in the brain are lacking, thus hampering progress towards the development of novel antiviral strategies and biomarkers of disease activity. Towards the aim of biomarker development extracellular vesicles (EVs) were isolated from JCPyV-infected and mock-infected human iPSC-derived astrocytes and analyzed by LC-MS/MS. As a inflammatory control, EVs were also isolated from cytokine-stimulated iPSC-derived astrocytes. We demonstrate that the proteomic signature associated with EVs from JCPyV-infected astrocytes reflect what was observed on a cellular level for infected astrocytes while being strikingly different from that of EVs generated under inflammatory conditions.

2023-08-28 | PXD044784 | Pride

JC Polyomavirus Infection of Primary Human Renal Epithelial Cells Is Controlled by a Type I IFN-Induced Response

Project description:JC polyomavirus (JCPyV) established a persistent infection, but BK polyomavirus (BKPyV) killed the cells in 15 days. To identify the cellular factors responsible for controlling JCPyV infection and promoting viral persistence, we profiled the transcriptomes of JCPyV- and BKPyV-infected cells at several time points postinfection. We found that interferon-stimulated genes (ISGs) were only activated in the JCPyV and not in the BKPyV-infected cells.

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Origin of JC polyomavirus variants associated with progressive multifocal leukoencephalopathy.

Project description:JC polyomavirus (JCV) DNAs from the urine of nonimmunocompromised individuals (designated archetypal isolates) regularly contain a regulatory sequence that may have generated various regulatory sequences of JCV isolates derived from the brain of patients with progressive multifocal leukoencephalopathy (PML). In this report, we constructed a phylogenetic tree for 14 isolates (7 archetypes and 7 PML types) from DNA sequence data on the VP1 (major capsid protein) gene. According to the phylogenetic tree, the 14 isolates diverged into types A and B, each of which contained archetypal and PML-type isolates. Each type further diverged into several groups containing archetypal and PML-type isolates. We conclude that PML-type isolates are polyphyletic in their origin and do not constitute a unique lineage. This conclusion suggests that PML-type JCV isolates are generated from archetypal strains during persistence in the hosts. Furthermore, the present phylogenetic analysis indicates that an ancestral JCV carried the archetypal regulatory sequence and that this structure has been conserved in the course of JCV evolution.

| S-EPMC46654 | biostudies-other

JC Polyomavirus Modifies the Expression of Human microRNAs in Progressive Multifocal Leukoencephalopathy Brain.

Project description:Progressive multifocal leukoencephalopathy (PML) is a severe neurological condition caused by reactivation of JC polyomavirus (JCPyV) in immunosuppression. Asymptomatic JCPyV persists in peripheral tissues. Upon reactivation, neurotropic rearrangements may emerge, and the virus gains access to the brain. To assess the mechanisms of PML pathogenesis, brain tissue material from PML patients was collected for small RNA sequencing. Upregulation of 8 microRNAs (miRNAs) in PML brain was validated using quantitative microRNA polymerase chain reaction (PCR). Bioinformatics tools were utilized to identify major associations of the upregulated miRNAs: neuroinflammation and blood-brain barrier disruption. The results indicate involvement of human miRNA regulation in PML pathogenesis.

| S-EPMC10547454 | biostudies-literature

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