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Progressive multifocal leukoencephalopathy (PML) is a rare neurological condition associated with reactivation of dormant JC polyomavirus (JCPyV). In this study, we characterized gene expression and JCPyV rearrangements in PML brain tissue. Infection of white matter astrocytes and oligodendrocytes as well as occasional brain cortex neurons was shown. PML brain harbored exclusively rearranged JCPyV variants. Viral transcripts covered the whole genome on both strands. Strong differential expression of human genes associated with neuroinflammation, blood-brain barrier permeability, and neurodegenerative diseases was shown. Pathway analysis revealed wide immune activation in PML brain. The study provides novel insights into the pathogenesis of PML. [ABSTRACT FROM AUTHOR]

The Epstein-Barr virus (EBV) is frequently found in endomyocardial biopsies (EMBs) from patients with heart failure, but the detection of EBV-specific DNA has not been associated with progressive hemodynamic deterioration. In this paper, we investigate the use of targeted next-generation sequencing (NGS) to detect EBV transcripts and their correlation with myocardial inflammation in EBV-positive patients with heart failure with reduced ejection fraction (HFrEF). Forty-four HFrEF patients with positive EBV DNA detection and varying degrees of myocardial inflammation were selected. EBV-specific transcripts from EMBs were enriched using a custom hybridization capture-based workflow and, subsequently, sequenced by NGS. The short-read sequencing revealed the presence of EBV-specific transcripts in 17 patients, of which 11 had only latent EBV genes and 6 presented with lytic transcription. The immunohistochemical staining for CD3+ T lymphocytes showed a significant increase in the degree of myocardial inflammation in the presence of EBV lytic transcripts, suggesting a possible influence on the clinical course. These results imply the important role of EBV lytic transcripts in the pathogenesis of inflammatory heart disease and emphasize the applicability of targeted NGS in EMB diagnostics as a basis for specific treatment. [ABSTRACT FROM AUTHOR]

Kaposi's sarcoma-associated herpesvirus is an oncogenic gammaherpesvirus that plays a major role in several human malignancies, including Kaposi's sarcoma, primary effusion lymphoma, and multicentric Castleman's disease. The complexity of KSHV biology is reflected in the sophisticated regulation of its biphasic life cycle, consisting of a quiescent latent phase and virion-producing lytic replication. KSHV expresses coding and noncoding RNAs, including microRNAs and long noncoding RNAs, which play crucial roles in modulating viral gene expression, immune evasion, and intercellular communication. Recent studies have highlighted the importance of RNA modifications, also known as the epitranscriptome, in regulating KSHV-encoded RNAs, adding a novel layer of posttranscriptional control previously unknown. These RNA modifications, such as N 6 -methyladenosine, A-to-I editing, and N 4 -acetylcytidine, are involved in fine-tuning KSHV gene expression during both latency and lytic replication. Understanding the role of RNA modifications in KSHV infection is essential for revealing new regulatory mechanisms and identifying therapeutic opportunities. Targeting these RNA modifications could serve as a strategy to disrupt key viral processes, offering promising insights into KSHV pathogenesis and therapeutic interventions., (© 2024 Wiley Periodicals LLC.)