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Kidney International Reports Jun 2024Earlier reports suggest that patients after ABO-incompatible kidney transplantation (ABOi) are at enhanced risk of developing BK-virus (BKV, also known as BK...
INTRODUCTION
Earlier reports suggest that patients after ABO-incompatible kidney transplantation (ABOi) are at enhanced risk of developing BK-virus (BKV, also known as BK polyomavirus [BKPyV]) nephropathy (BKPyVAN). It remains elusive whether this is a result of more intense immunosuppression or an ABOi-associated "intrinsic attribute." To address this question, we measured Torque Teno virus (TTV) loads as a quantitative proxy for immunosuppressive depth in ABOi recipients and compared them to human leukocyte antigen-incompatible (HLAi, i.e. pretransplant donor-specific antibody-positive) and standard-risk transplant recipients.
METHODS
Our retrospective study screened 2256 consecutive kidney transplantations performed between 2007 and 2020 at the Medical University of Vienna. Out of 629 in-principle eligible transplantations, we were able to include 465 patients: 42 ABOi, 106 HLAi, and 317 control recipients. Longitudinal TTV- polymerase chain reaction (PCR) and BKV-PCR was carried out at predefined timepoints and ranged from pretransplant until month 24 posttransplantation. TTV loads and immunosuppression were evaluated in the context of BKV-associated complications.
RESULTS
ABOi recipients had a higher TTV load compared to HLAi and controls both at month 3 (median 1.5 × 10 vs. 2.4 × 10 vs. 9.1 × 10; = 0.010) and at month 6 (3.1 × 10 vs. 1.4 × 10 vs. 6.4 × 10; = 0.014) posttransplantation. Tacrolimus exposure was significantly higher in ABOi patients compared to HLAi and control patients (ABOi vs. HLAi: = 0.007; ABOi vs. controls: < 0.0001). Biopsy-proven BKPyVAN was more frequent in ABOi recipients when compared to HLAi and control recipients (11.9% vs. 2.8% vs. 4.1%; = 0.046).
CONCLUSION
Our data support the assumption that ABOi patients are indeed at higher risk to develop BKPyVAN. A higher TTV load and immunosuppressive burden suggest that intense immunosuppression, rather than an "intrinsic attribute" conferred by ABOi, may contribute to this finding.
PubMed: 38899213
DOI: 10.1016/j.ekir.2024.04.003 -
Cancers May 2024Epstein-Barr virus (EBV), Kaposi sarcoma human virus (KSHV), human papillomavirus (HPV), hepatitis B and C viruses (HBV, HCV), human T-lymphotropic virus-1 (HTLV-1), and...
Epstein-Barr virus (EBV), Kaposi sarcoma human virus (KSHV), human papillomavirus (HPV), hepatitis B and C viruses (HBV, HCV), human T-lymphotropic virus-1 (HTLV-1), and Merkel cell polyomavirus (MCPyV) are the seven human oncoviruses reported so far. While traditionally viewed as a benign virus causing mild symptoms in healthy individuals, human cytomegalovirus (HCMV) has been recently implicated in the pathogenesis of various cancers, spanning a wide range of tissue types and malignancies. This perspective article defines the biological criteria that characterize the oncogenic role of HCMV and based on new findings underlines a critical role for HCMV in cellular transformation and modeling the tumor microenvironment as already reported for the other human oncoviruses.
PubMed: 38893091
DOI: 10.3390/cancers16111970 -
International Journal of Molecular... May 2024Cigarette smoking is a primary contributor to mortality risks and is associated with various diseases. Among these, COPD represents a significant contributor to global...
Cigarette smoking is a primary contributor to mortality risks and is associated with various diseases. Among these, COPD represents a significant contributor to global mortality and disability. The objective of this study is to investigate the effect of smoking on a selected battery of variables, with an emphasis on DNA damage. A total of 87 elderly patients diagnosed with COPD, divided into three groups based on their smoking history (current, former, never-smokers), were evaluated using a cross-sectional approach. Clinical features including mortality and inflammatory/oxidative parameters (Lymphocytes/Monocytes, Neutrophils/Lymphocytes, Platelets/Lymphocytes ratio), SII, MDA, 8-Oxo-dG, and IL6 (ELISA assay), as well as DNA damage (comet assay), were investigated. Virus infection, i.e., influenza A virus subtype H1N1, JC polyomavirus (JCPyV), BK polyomavirus (BKPyV), and Torquetenovirus (TTV), was also tested. Current smokers exhibit higher levels of comorbidity (CIRS; < 0.001), Platelets/Lymphocytes ratio ( < 0.001), systemic immune inflammation ( < 0.05), and DNA damage ( < 0.001). Former smokers also showed higher values for parameters associated with oxidative damage and showed a much lower probability of surviving over 5 years compared to never- and current smokers ( < 0.0017). This study showed a clear interaction between events which are relevant to the oxidative pathway and cigarette smoking. A category of particular interest is represented by former smokers, especially for lower survival, possibly due to the presence of more health problems. Our findings raise also the attention to other parameters which are significantly affected by smoking and are useful to monitor COPD patients starting a program of pulmonary rehabilitation (DNA damage, inflammation parameters, and selected viral infections).
Topics: Humans; Pulmonary Disease, Chronic Obstructive; Male; Female; Aged; Cigarette Smoking; DNA Damage; Oxidative Stress; Cross-Sectional Studies; Middle Aged; Biomarkers; Inflammation
PubMed: 38892022
DOI: 10.3390/ijms25115834 -
Frontiers in Cellular and Infection... 2024Extracellular vesicles (EVs) are membrane-bound vesicles secreted by all cell types that play a central role in cell-to-cell communication. Since these vesicles serve as... (Review)
Review
Extracellular vesicles (EVs) are membrane-bound vesicles secreted by all cell types that play a central role in cell-to-cell communication. Since these vesicles serve as vehicles of cellular content (nucleic acids, proteins and lipids) with the potential to cross biological barriers, they represent a novel attractive window into an otherwise inaccessible organ, such as the brain. The composition of EVs is cell-type specific and mirrors the physiological condition of the cell-of-origin. Consequently, during viral infection, EVs undergo significant changes in their content and morphology, thereby reflecting alterations in the cellular state. Here, we briefly summarize the potential of brain-derived EVs as a lens into viral infection in the central nervous system, thereby: 1) uncovering underlying pathophysiological processes at play and 2) serving as liquid biopsies of the brain, representing a non-invasive source of biomarkers for monitoring disease activity. Although translating the potential of EVs from research to diagnosis poses complexities, characterizing brain-derived EVs in the context of viral infections holds promise to enhance diagnostic and therapeutic strategies, offering new avenues for managing infectious neurological diseases.
Topics: Extracellular Vesicles; Humans; Biomarkers; Brain; Virus Diseases; Animals; Cell Communication
PubMed: 38887492
DOI: 10.3389/fcimb.2024.1423394 -
Infection, Genetics and Evolution :... Jun 2024The Eurasian beaver (Castor fiber), native to Hungary, faced local extinction in 1865 and was successfully reintroduced between mid-1980s and 2008. Despite screening...
The Eurasian beaver (Castor fiber), native to Hungary, faced local extinction in 1865 and was successfully reintroduced between mid-1980s and 2008. Despite screening programs focusing on animal health during reintroduction in other countries, information about viruses in the Hungarian beaver population remains limited. Polyomaviruses (PyVs) have been identified in various rodents, and have been detected just recently in beavers by us. In this paper we present the full genome analysis of the first PyV detected in Eurasian beaver. The novel PyV was discovered in the kidney tissues of two specimens. The genome is 5244 bp, and contains four genes. Small T-antigen (STAg) and alternative large T ORF (ALTO) genes are directly fused together forming the middle T-antigen (MTAg). VP3 is absent from the genome. Its large T-antigen (LTAg) coding sequence exhibited over 15% genetic divergence from known PyVs, supporting its classification into a new species within the genus Alphapolyomavirus, suggesting to be named Alphapolyomavirus castoris. Phylogenetic analysis, based on the LTAg gene showed, that the beaver PyV forms a distinct clade with primate PyVs within the genus Alphapolyomavirus, separate from other rodent PyVs. Phylogenetic study of the VP1 gene however showed this virus to belong in a distinct clade with the same primate PyVs, and additionally PyVs from rodents and a myocastor, which suggest host virus co-evolution. The virus detection of the euthanized beavers suggests an apathogenic persistent infections. The aquatic lifestyle of beavers may influence virus transmission, warranting further exploration of undiscovered viruses in beavers.
PubMed: 38876268
DOI: 10.1016/j.meegid.2024.105620 -
Microbiology Spectrum Jun 2024The human polyomavirus, JCPyV, establishes a lifelong persistent infection in the peripheral organs of a majority of the human population worldwide. Patients who are...
JCPyV infection of primary choroid plexus epithelial cells reduces expression of critical junctional proteins and increases expression of barrier disrupting inflammatory cytokines.
UNLABELLED
The human polyomavirus, JCPyV, establishes a lifelong persistent infection in the peripheral organs of a majority of the human population worldwide. Patients who are immunocompromised due to underlying infections, cancer, or to immunomodulatory treatments for autoimmune disease are at risk for developing progressive multifocal leukoencephalopathy (PML) when the virus invades the CNS and infects macroglial cells in the brain parenchyma. It is not yet known how the virus enters the CNS to cause disease. The blood-choroid plexus barrier is a potential site of virus invasion as the cells that make up this barrier are known to be infected with virus both and . To understand the effects of virus infection on these cells we challenged primary human choroid plexus epithelial cells with JCPyV and profiled changes in host gene expression. We found that viral infection induced the expression of proinflammatory chemokines and downregulated junctional proteins essential for maintaining blood-CSF and blood-brain barrier function. These data contribute to our understanding of how JCPyV infection of the choroid plexus can modulate the host cell response to neuroinvasive pathogens.
IMPORTANCE
The human polyomavirus, JCPyV, causes a rapidly progressing demyelinating disease in the CNS of patients whose immune systems are compromised. JCPyV infection has been demonstrated in the choroid plexus both and and this highly vascularized organ may be important in viral invasion of brain parenchyma. Our data show that infection of primary choroid plexus epithelial cells results in increased expression of pro-inflammatory chemokines and downregulation of critical junctional proteins that maintain the blood-CSF barrier. These data have direct implications for mechanisms used by JCPyV to invade the CNS and cause neurological disease.
PubMed: 38874395
DOI: 10.1128/spectrum.00628-24 -
Journal of Medical Virology Jun 2024Polyomaviruses BK (BKPyV) and JC (JCPyV), belonging to the Polyomaviridae, are responsible for human pathologies. In kidney transplant recipients, BKPyV replication can...
Polyomaviruses BK (BKPyV) and JC (JCPyV), belonging to the Polyomaviridae, are responsible for human pathologies. In kidney transplant recipients, BKPyV replication can lead to irreversible nephron damage whereas JCPyV replication remains asymptomatic. Concomitant replication is rare and potential competition between the infections has been described. The aim of this retrospective case-control study was to describe the molecular epidemiology and risk factors associated with BKPyV and JCPyV replication in a cohort of kidney transplant recipients. In total, 655 urine samples from 460 patients were tested for BKPyV and JCPyV DNA. Positive samples were submitted to strain genotyping. Demographic and clinical characteristics were also compared. Isolated JCPyV and BKPyV was found in 16.5% and 23.3% of patients, respectively; co-replication was rare (3.9%). BKPyV strains Ib-2, Ib-1, and IVc-2 were the most prevalent. JCPyV strains mostly belonged to genotypes 4 and 1B. During follow-up, JCPyV shedding significantly reduced the risk of BKPyV DNAuria, with an odds ratio of 0.57 (95% confidence interval: 0.35-0.99), and was associated with better prognosis than BKPyV replication, based on the estimated glomerular filtration rate. Molecular epidemiology of BKPyV and JCPyV strains in our region was similar to previous studies. This study suggests that JCPyV is benign and appears to limit damaging BKPyV replication. JCPyV DNAuria screening could thus be a useful strategy to predict BKPyV-related outcomes.
Topics: Humans; BK Virus; Polyomavirus Infections; Kidney Transplantation; Male; Female; Middle Aged; Retrospective Studies; Risk Factors; JC Virus; Case-Control Studies; Adult; Genotype; Molecular Epidemiology; Virus Shedding; Aged; Transplant Recipients; Tumor Virus Infections; DNA, Viral; Allografts
PubMed: 38874263
DOI: 10.1002/jmv.29742 -
PloS One 2024Colorectal cancer (CRC) is a cancer type that is thought to be influenced by human papillomaviruses (HPVs) and human polyomaviruses (HPyVs). In Egypt, CRC ranks as the...
BACKGROUND
Colorectal cancer (CRC) is a cancer type that is thought to be influenced by human papillomaviruses (HPVs) and human polyomaviruses (HPyVs). In Egypt, CRC ranks as the 7th most common cancer, accounting for 3.47% of male cancers and 3% of female cancers. However, there is currently a lack of information regarding the presence of PyVs and HPVs co-infection specifically in CRC cases in Egypt. Therefore, the aim of this study was to investigate the occurrence of HPVs and HPyVs (JCPyV, BKPyV, and SV40) infections, as well as co-infections, among CRC patients in Egypt. Additionally, the study aimed to assess any potential association between these viral infections and tumor stages.
METHODS
In the present study, we analyzed a total of 51 tissue samples obtained from Egyptian CRC patients, along with 19 polyps' samples. Our investigation focused on the detection and genotyping of HPyVs using Real-Time PCR. Additionally, we employed real-time PCR for the detection of HPVs, and for their genotyping, we utilized a combination of PCR amplification followed by sequencing.
RESULTS
In our study, we found evidence of HPyVs infection in the CRC patients, specifically SV40 (25.5%) and BKPyV (19.6%). However, JCPyV was not detected in the samples that were examined. Additionally, we discovered that HPV was present in 43.1% of the CRC patients. When considering viral co-infections, 19.6% of the CRC samples showed coexistence of multiple viruses, while no co-infections were found in the polyps samples. Importantly, we observed a significant correlation between the presence of HPVs and advanced colorectal tumor grades B2 and D.
CONCLUSION
Our findings provide valuable data for the detection of oncogenic viruses in colorectal cancer (CRC) and underscore the association of viral co-infections with advanced tumor stages. However, further research with larger cohorts is necessary to validate these findings and strengthen their significance in the field of CRC.
Topics: Humans; Colorectal Neoplasms; Egypt; Female; Male; Middle Aged; Polyomavirus Infections; Papillomavirus Infections; Polyomavirus; Papillomaviridae; Case-Control Studies; Coinfection; Aged; Adult; Tumor Virus Infections; Genotype
PubMed: 38861564
DOI: 10.1371/journal.pone.0304147 -
Virus Research Aug 2024The human JC polyomavirus (JCV) is a widespread, neurotropic, opportunistic pathogen responsible for progressive multifocal leukoencephalopathy (PML) as well as other...
The human JC polyomavirus (JCV) is a widespread, neurotropic, opportunistic pathogen responsible for progressive multifocal leukoencephalopathy (PML) as well as other diseases in immunosuppressed individuals, including granule cell neuronopathy, JCV-associated nephropathy, encephalitis, and meningitis in rare cases. JCV classification is still unclear, where the ICTV (International Committee on Taxonomy of Viruses) has grouped all the strains into human polyomavirus 2, with no classification on clade and subclade levels. Therefore, JCV strains were previously classified using different genomic regions, e.g., full-length, VP1, and the V-T intergenic region etc., and the strains were grouped into several types related to various geographic locations and human ethnicities. However, neither of these classifications and nomenclature contemplates all the groups described so far. Herein, we evaluated all the available full-length coding genomes, VP1, and large T antigen nucleotide sequences of JCV reported during 1993-2023 and classified them into four major phylogenetic clades, i.e., GI-GIV, where GI is further grouped into two types GI.1 and GI.2 with five sub-clades each (GI.1/GI.2 a-e), GII into three (GII a-c), GIII as a separate clade, and GIV into seven sub-clades (GIV a-g). Similarly, the phylogeographic network analysis indicated four major clusters corresponding to GI-GIV clades, each with multiple subclusters and mutational sub-branches corresponding to the subclades. GI and GIV clusters are connected via GI.1-e reported from Europe and America, GII, GIII and GIV clusters are connected by GII-b and GII-c strains reported from Africa, while GIV cluster strains are connected to the Russia-Italy JCV haplotype. Furthermore, we identified JCV-variant-GS/B-Germany-1997 (GenBank ID: AF004350.1) as an inter-genotype recombinant having major and minor parents in the GI.1-e and GII-a clades, respectively. Additionally, the amino acid variability analysis revealed high entropy across all proteins. The large T antigen exhibited the highest variability, while the small t antigen showed the lowest variability. Our phylogenetic and phylogeographic analyses provide a new approach to genotyping and sub-genotyping and present a comprehensive classification system of JCV strains based on their genetic characteristics and geographic distribution, while the genetic recombination and amino acid variability can help identify pathogenicity and develop effective preventive and control measures against JCV infections.
Topics: JC Virus; Phylogeography; Humans; Phylogeny; Genome, Viral; Leukoencephalopathy, Progressive Multifocal; Polyomavirus Infections; Genetic Variation; Cluster Analysis
PubMed: 38848817
DOI: 10.1016/j.virusres.2024.199414 -
Annales de Pathologie Jun 2024Cutaneous adnexal tumours are a heterogeneous group of epithelial lesions that includes tumours with follicular, sudoral and/or sebaceous differentiation, or even...
Cutaneous adnexal tumours are a heterogeneous group of epithelial lesions that includes tumours with follicular, sudoral and/or sebaceous differentiation, or even several combined lines of differentiation. Over the last few years, molecular analysis of these lesions has allowed to identify specific molecular events responsible for tumour development in an increasing number of tumour types. Like other rare neoplasms, such as soft tissue tumours, adnexal tumours display fusion genes resulting from chromosomal translocations that may be specific for the diagnosis if molecular data are properly integrated in the clinical and morphological setting. Molecular testing of adnexal tumours is valuable as it allows to strengthen the robustness of the diagnosis for a group of tumours displaying a wide morphological spectrum. It has allowed to refine the diagnostic criteria and to develop increasingly specific diagnostic immunostainings. Finally, molecular testing has been responsible for the identification of new entities or morphological subtypes of previously known entities. The aim of this review is to provide an update on cutaneous adnexal tumours associated with fusion genes and to evaluate the impact of molecular data on the diagnosis of these lesions.
PubMed: 38839526
DOI: 10.1016/j.annpat.2024.05.002