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Biomedicines May 2024BK polyomavirus (BKPyV) is still a real threat in the management of kidney transplantation. Immunosuppressive treatment disrupts the equilibrium between virus... (Review)
Review
BK polyomavirus (BKPyV) is still a real threat in the management of kidney transplantation. Immunosuppressive treatment disrupts the equilibrium between virus replication and immune response, and uncontrolled BKPyV replication leads to nephropathy (BKPyV nephropathy). The first evidence of BKPyV reactivation in transplant recipients is the detection of viral shedding in urine, which appears in 20% to 60% of patients, followed by BKPyV viremia in 10-20% of kidney transplant recipients. BKPyV nephropathy eventually occurs in 1-10% of this population, mainly within the first 2 years post-transplantation, causing graft loss in about half of those patients. Few data exist regarding the pediatric population and we focus on them. In this paper, we review the existing diagnostic methods and summarize the evidence on the role of BKPyV humoral and cellular immunity in modulating the clinical course of BKPyV infection and as potential predictors of the outcome. We look at the known risk factors for BKPyV nephropathy in the immunosuppressed patient. Finally, we propose a sensible clinical attitude in order to screen and manage BKPyV infection in kidney transplant children.
PubMed: 38791055
DOI: 10.3390/biomedicines12051093 -
Virchows Archiv : An International... May 2024
PubMed: 38789627
DOI: 10.1007/s00428-024-03831-7 -
Diseases (Basel, Switzerland) May 2024Progressive Multifocal Leukoencephalopathy (PML) is a possibly fatal demyelinating disease and John Cunningham Polyomavirus (JCPyV) is believed to cause this condition.... (Review)
Review
Progressive Multifocal Leukoencephalopathy (PML) is a possibly fatal demyelinating disease and John Cunningham Polyomavirus (JCPyV) is believed to cause this condition. The so-called JCPyV was initially reported in lymphoma and Human Immunodeficiency Virus (HIV) cases, whereas nowadays, its incidence is increasing in Multiple Sclerosis (MS) cases treated with natalizumab (Tysabri). However, there are conflicting literature data on its pathology and diagnosis, whereas some misdiagnosed reports exist, giving rise to further questions towards the topic. In reality, the so-called PML and the supposed JCPyV are not what they seem to be. In addition, novel and more frequent PML-like conditions may be reported, especially after the Coronavirus Disease 2019 (COVID-19) pandemic.
PubMed: 38785755
DOI: 10.3390/diseases12050100 -
Current Oncology (Toronto, Ont.) May 2024This case report describes the development of Progressive Multifocal Leukoencephalopathy (PML) in a 72-year-old male with relapsed/refractory multiple myeloma (RRMM),...
This case report describes the development of Progressive Multifocal Leukoencephalopathy (PML) in a 72-year-old male with relapsed/refractory multiple myeloma (RRMM), following a single dose of teclistamab amidst a COVID-19 infection. Shortly after starting teclistamab treatment, the patient developed symptoms, including fever, altered mental status, and right-sided paresis. A diagnosis of PML was confirmed through the detection of JC virus PCR in the cerebrospinal fluid. Our report emphasizes the occurrence of PML after only one dose of teclistamab and highlights teclistamab's potential for severe infectious complications, despite its promise in treating RRMM.
Topics: Humans; Leukoencephalopathy, Progressive Multifocal; Multiple Myeloma; Male; Aged; COVID-19; JC Virus; SARS-CoV-2
PubMed: 38785483
DOI: 10.3390/curroncol31050202 -
Histopathology May 2024Porocarcinoma is a malignant sweat gland tumour differentiated toward the upper part of the sweat duct and may arise from the transformation of a preexisting benign...
AIMS
Porocarcinoma is a malignant sweat gland tumour differentiated toward the upper part of the sweat duct and may arise from the transformation of a preexisting benign poroma. In 2019, Sekine et al. demonstrated the presence of YAP1::MAML2 and YAP1::NUTM1 fusions in most poromas and porocarcinomas. Recently, our group identified PAK2-fusions in a subset of benign poromas. Herein we report a series of 12 porocarcinoma cases harbouring PAK1/2/3 fusions.
METHODS AND RESULTS
Five patients were male and the median age was 79 years (ranges: 59-95). Tumours were located on the trunk (n = 7), on the thigh (n = 3), neck (n = 1), or groin area (n = 1). Four patients developed distant metastases. Microscopically, seven cases harboured a benign poroma component and a malignant invasive part. Ductal formations were observed in all, while infundibular/horn cysts and cells with vacuolated cytoplasm were detected in seven and six tumours, respectively. In three cases, the invasive component consisted of a proliferation of elongated cells, some of which formed pseudovascular spaces, whereas the others harboured a predominant solid or trabecular growth pattern. Immunohistochemical staining for CEA and EMA confirmed the presence of ducts. Focal androgen receptor expression was detected in three specimens. Whole RNA sequencing evidenced LAMTOR1::PAK1 (n = 2), ZDHHC5::PAK1 (n = 2), DLG1::PAK2, CTDSP1::PAK1, CTNND1::PAK1, SSR1::PAK3, CTNNA1::PAK2, RNF13::PAK2, ROBO1::PAK2, and CD47::PAK2. Activating mutation of HRAS (G13V, n = 3, G13R, n = 1, Q61L, n = 2) was present in six cases.
CONCLUSION
Our study suggests that PAK1/2/3 fusions is the oncogenic driver of a subset of porocarcinomas lacking YAP1 rearrangement.
PubMed: 38785043
DOI: 10.1111/his.15214 -
Ethiopian Journal of Health Sciences Jul 2023This review aims to determine the potential role of Merkel Cell Polyomavirus (MCPyV) in the pathogenesis of cervical squamous cell carcinomas and adenocarcinomas. (Review)
Review
BACKGROUND
This review aims to determine the potential role of Merkel Cell Polyomavirus (MCPyV) in the pathogenesis of cervical squamous cell carcinomas and adenocarcinomas.
METHODS
A PRISMA systematic search appraisal was conducted. The Scopus, Web of Science, PubMed, EMBASE, Google Scholar, and MEDLINE databases for publications in English were searched up to September 2022 for all relevant articles. All articles that have outlined the contributions of the MCPyV to cervical squamous cell carcinomas and adenocarcinomas were included.
RESULTS
The six databases produced 6806 articles. Only six articles met the inclusion criteria and were included. The protocol of this review was submitted and registered with the PROSPERO (Code no. CRD42022369197). The total sample size across the articles was 1135; the age of the participants ranged between 18 and 75 years. In addition, the included articles were conducted between 2012 to 2016. All included articles have a cross-sectional design.Furthermore, different kinds of samples were collected in the reviewed articles, namely cervical tissue biopsies, cervical smears, formalin-fixed paraffin-embedded resection specimens, and cervical adenocarcinomas. Moreover, five articles showed no statistically significant association between the MCPyV and cervical squamous cell carcinomas and adenocarcinomas. In contrast, one article revealed a positive association between MCPyV and cervical squamous cell carcinomas and adenocarcinomas.
CONCLUSIONS
MCPyV could not be associated with the pathogenesis of cervical squamous cell carcinomas and adenocarcinomas. Further attention should be given to examining this association, and further studies with a large sample size are recommended to confirm these findings.
Topics: Humans; Female; Uterine Cervical Neoplasms; Carcinoma, Squamous Cell; Adenocarcinoma; Polyomavirus Infections; Merkel cell polyomavirus; Tumor Virus Infections; Middle Aged; Adult; Aged
PubMed: 38784202
DOI: 10.4314/ejhs.v33i4.18 -
Journal of Neurovirology May 2024Progressive multifocal leukoencephalopathy (PML) is an opportunistic infectious demyelinating disease of the central nervous system caused by JC polyomavirus...
Progressive multifocal leukoencephalopathy (PML) is an opportunistic infectious demyelinating disease of the central nervous system caused by JC polyomavirus predominantly affecting immunocompromised individuals. Nowadays, HIV, hematological malignancies and iatrogenic immune suppression account for most PML cases. For unknown reasons, spinal cord is classically protected from PML lesions. Here, we report the course of a patient harboring spinal cord lesions in the context of PML with immune reconstitution inflammatory syndrome and review the eight other cases reported in the literature so far. Then, we discuss the evolving spectrum of PML over recent years, potentially making its diagnosis more challenging.
PubMed: 38778006
DOI: 10.1007/s13365-024-01213-y -
Journal of the Neurological Sciences Jun 2024Progressive multifocal leukoencephalopathy (PML) is a potentially life-threatening complication among Multiple Sclerosis (MS) patients under natalizumab treatment, with...
Association of B-cell activating factor gene variants with serum anti-JCV antibody positivity in male patients with multiple sclerosis under natalizumab treatment: Implications for progressive multifocal leukoencephalopathy risk stratification.
INTRODUCTION
Progressive multifocal leukoencephalopathy (PML) is a potentially life-threatening complication among Multiple Sclerosis (MS) patients under natalizumab treatment, with serum anti-JCV antibody titers being used for stratification risk. Given the critical role of interferon (IFN)/B-cell activating factor (BAFF) axis in humoral immune responses against viruses, we explored whether it is involved in the generation of serum anti-JCV antibodies among these patients.
METHODS
162 consecutive patients with relapsing-remitting MS under natalizumab treatment were included. Serum anti-JCV antibodies were measured at baseline, as well as 12 and 24 months after treatment initiation. Type I and II IFN-inducible genes and BAFF expression were quantitated in peripheral blood by qRT-PCR. Moreover, BAFF rs9514828, rs1041569, and rs9514827 gene variants were assessed by RFLP-PCR.
RESULTS
While type I and II IFN inducible gene expression were not associated with anti-JCV serum titers, the latter were significantly correlated with BAFF gene expression. Of interest, the TTT haplotype of the studied BAFF variants was more frequently detected in male, but not female anti-JCV (+) MS patients compared to anti-JCV (-) counterparts at baseline, as well as at 12 months and 24 months of natalizumab treatment. Measures of clinical validity/utility for the BAFF TTT haplotype showed 88% specificity, 45%, positive predictive value, and sensitivity of 70% for the discrimination of anti-JCV (+) male MS patients after 24 months of treatment.
CONCLUSIONS
Our study suggests an implication of the BAFF axis in the production of serum anti-JCV antibodies. Additionally, the BAFF TTT haplotype derived from the rs9514828, rs1041569, and rs9514827 variants may represent a novel risk factor for anti-JCV seropositivity and indirectly for PML development among male MS patients treated with natalizumab.
Topics: Humans; Natalizumab; B-Cell Activating Factor; Male; Leukoencephalopathy, Progressive Multifocal; Adult; Female; Immunologic Factors; JC Virus; Multiple Sclerosis, Relapsing-Remitting; Middle Aged; Antibodies, Viral; Polymorphism, Single Nucleotide
PubMed: 38761670
DOI: 10.1016/j.jns.2024.123046 -
European Archives of... May 2024Sinonasal lymphoma (SL) is a rare lymphatic neoplasm of the nasal cavities, paranasal sinuses and nasopharynx. Whereas some risk factors for SL subtypes have been...
PURPOSE
Sinonasal lymphoma (SL) is a rare lymphatic neoplasm of the nasal cavities, paranasal sinuses and nasopharynx. Whereas some risk factors for SL subtypes have been identified, their aetiology is unknown. Along with other predisposing factors, the viral association of lymphomas, such as Epstein-Barr virus (EBV) and Burkitt and Hodgkin lymphomas, is well-established. Modern molecular biology techniques have enabled the discovery of novel human viruses, exemplified by the protoparvovirus cutavirus (CuV), associated with cutaneous T-cell lymphoma. These findings, and the anatomical location of the sinonasal tract with its rich microbiome and infectious agents, justify in-depth studies among SL.
METHODS
We analysed the presence of 20 viruses of Orthoherpesviridae, Parvoviridae, and Polyomaviridae by qPCR in 24 SL tumours. We performed RNAscope in situ hybridisation (RISH) to localize the viruses. Parvovirus-specific IgG was analysed by enzyme immunoassay and targeted next-generation sequencing (NGS) was applied to detect CuV in plasma.
RESULTS
We detected viral DNA in 15/24 (63%) tumours; nine of EBV, six of human herpesvirus (HHV) -7, four each of HHV-6B and parvovirus B19, two of cytomegalovirus, and one each of CuV and Merkel-cell polyomavirus. We found tumours with up to four viruses per tumour, and localized CuV and EBV DNAs by RISH. Two of the ten plasma samples exhibited CuV IgG, and one plasma sample demonstrated CuV viremia by NGS.
CONCLUSION
Viruses were frequent findings in SL. The EBV detection rate was high in diffuse large B-cell lymphoma, and co-detections with other viruses were prevalent.
PubMed: 38758242
DOI: 10.1007/s00405-024-08702-0 -
BMC Veterinary Research May 2024Primary sheep fetal fibroblasts (SFFCs) have emerged as a valuable resource for investigating the molecular and pathogenic mechanisms of orf viruses (ORFV). However,...
BACKGROUND
Primary sheep fetal fibroblasts (SFFCs) have emerged as a valuable resource for investigating the molecular and pathogenic mechanisms of orf viruses (ORFV). However, their utilization is considerably restricted due to the exorbitant expenses associated with their isolation and culture, their abbreviated lifespan, and the laborious procedure.
RESULTS
In our investigation, the primary SFFCs were obtained and immortalized by introducing a lentiviral recombinant plasmid containing the large T antigen from simian virus 40 (SV40). The expression of fibronectin and vimentin proteins, activity of SV40 large T antigen, cell proliferation assays, and analysis of programmed cell death revealed that the immortalized large T antigen SFFCs (TSFFCs) maintained the same physiological characteristics and biological functions as the primary SFFCs. Moreover, TSFFCs demonstrated robust resistance to apoptosis, extended lifespan, and enhanced proliferative activity compared to primary SFFCs. Notably, the primary SFFCs did not undergo in vitro transformation or exhibit any indications of malignancy in nude mice. Furthermore, the immortalized TSFFCs displayed live ORFV vaccine susceptibility.
CONCLUSIONS
Immortalized TSFFCs present valuable in vitro models for exploring the characteristics of ORFV using various techniques. This indicates their potential for secure utilization in future studies involving virus isolation, vaccine development, and drug screening.
Topics: Animals; Fibroblasts; Sheep; Mice; Orf virus; Mice, Nude; Cell Proliferation; Simian virus 40; Cell Line; Apoptosis; Antigens, Viral, Tumor
PubMed: 38745180
DOI: 10.1186/s12917-024-04054-3