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Indian Journal of Nephrology 2022Polyomavirus nephropathy (PVN) is a known complication of renal transplantation due to the reactivation of latent BK virus (BKV) infection. Viral replication is usually...
Polyomavirus nephropathy (PVN) is a known complication of renal transplantation due to the reactivation of latent BK virus (BKV) infection. Viral replication is usually confined to tubules. However, in severe viremia and late stages of PVN, it can involve glomerular parietal epithelial cells. Glomerular involvement by BKV can cause crescent formation and may lead to graft failure. We describe a relatively rare case of PVN with glomerular involvement and crescent formation in a 52-year-old male who had undergone a transplant 16 months ago. Despite the stoppage of immunosuppression, graft failure occurred eventually. Interestingly, we observed the intense positivity for IgG and c4d in the Bowman capsule on immunofluorescence. Observation of such positivity along Bowman capsule in renal biopsies with a limited number of glomeruli should alert pathologists to do a vigilant search of BKV inclusion and perform immunohistochemistry for SV 40 large T antigen.
PubMed: 36704584
DOI: 10.4103/ijn.ijn_336_21 -
Frontiers in Medicine 2022BK virus is a common opportunistic viral infection that could cause BK virus-associated nephropathy in renal transplant recipients. Thus, we retrospectively analyzed...
BK virus is a common opportunistic viral infection that could cause BK virus-associated nephropathy in renal transplant recipients. Thus, we retrospectively analyzed clinical and laboratory data associated with a higher risk of BK virus activation from 195 renal transplant recipients by the multivariate logistic regression analysis and performed the external validation. Results showed that patients with BK virus active infection were associated with a deceased donor, had lower direct bilirubin levels, a higher proportion of albumin in serum protein electrophoresis, and lower red blood cells and neutrophil counts. The multivariate logistic regression analyses revealed that the living donor, direct bilirubin, and neutrophil counts were significantly associated with BK virus activation. The logistic regression model displayed a modest discriminability with the area under the receiver operating characteristic curve of 0.689 (95% CI: 0.607-0.771; < 0.01) and also demonstrated a good performance in the external validation dataset (the area under the receiver operating characteristic curve was 0.699, 95% CI: 0.5899-0.8081). The novel predictive nomogram achieved a good prediction of BK virus activation in kidney transplant recipients.
PubMed: 35223891
DOI: 10.3389/fmed.2022.770699 -
Viruses Jan 2022The BK polyomavirus (BKPyV) is a widespread pathogen in humans. Polymorphism of the region encoding the VP1 protein of BKPyV provides the basis for classifying the virus...
The BK polyomavirus (BKPyV) is a widespread pathogen in humans. Polymorphism of the region encoding the VP1 protein of BKPyV provides the basis for classifying the virus into types and subtypes, whose frequency varies depending on geographic location. The aim of our study was to determine the frequency of BKPyV in the Polish population and to assess its variation by analysing polymorphism in the typing region. The study was conducted on 168 healthy, Polish volunteers, whose blood (plasma) and urine were sampled. The virus was detected using PCR, products, sequenced and subjected to bioinformatic analysis. In addition, viral load was assessed by qPCR. The presence of the genetic material of the BK virus was noted in 61/168 urine samples but in none of the plasma sample. Sequencing and phylogenetic analysis confirmed that the BKPyV isolates were of types I and IV, dominant in Europe (63.93% and 36.07%, respectively). All isolates from genotype I belonged to subtype Ib-2, showing polymorphism at position 1809 with a frequency of 61.54% (G1809A) and 38.46% (G1809C). To the best of our knowledge, this is the first study of this magnitude on the genetic variation of BKPyV among healthy volunteers in Poland.
Topics: Adult; Aged; BK Virus; Base Sequence; DNA, Viral; Europe; Female; Genetic Variation; Genotype; Humans; Male; Middle Aged; Molecular Epidemiology; Phylogeny; Poland; Polyomavirus Infections; Viral Load
PubMed: 35215804
DOI: 10.3390/v14020209 -
Cancer Immunology, Immunotherapy : CII Aug 2020The etiological role of human papillomavirus (HPV) in oropharyngeal squamous cell carcinoma (OPSCC) is confirmed. However, the role of other oncoviruses in OPSCC is...
BACKGROUND
The etiological role of human papillomavirus (HPV) in oropharyngeal squamous cell carcinoma (OPSCC) is confirmed. However, the role of other oncoviruses in OPSCC is unknown.
MATERIALS AND METHODS
A total of 158 consecutive OPSCC patients treated with curative intent were included. DNA extracted from tumor sections was used to detect Epstein-Barr virus (EBV), HPV, and the following polyomaviruses: John Cunningham virus (JCV), Simian virus 40 (SV40), and BK virus (BKV) with PCR. In addition, p16 expression was studied by immunohistochemistry, and EBV-encoded small RNA (EBER) transcripts were localized by in situ hybridization. The effect of viral status on overall survival (OS) and disease-free survival (DFS) was analyzed.
RESULTS
A total of 94/158 samples (59.5%) were HPV-positive, 29.1% contained BKV DNA, 20.3% EBV DNA, 13.9% JCV DNA, and 0.6% SV40 DNA. EBER was expressed only in stromal lymphocytes adjacent to the tumor and correlated with HPV positivity (p = 0.026). p16 expression associated only with HPV. None of the three polyomaviruses had an impact on survival. Patients with EBER-positive but HPV-negative OPSCC had significantly poorer OS and DFS than those with HPV-positive OPSCC and slightly worse prognosis compared with the patients with EBER-negative and HPV-negative OPSCC.
CONCLUSION
Polyomaviruses are detectable in OPSCC but seem to have no impact on survival, whereas HPV was the strongest viral prognostic factor. EBER expression, as a sign of latent EBV infection, may have prognostic impact among patients with HPV-negative OPSCC. EBER analysis may identify a new subgroup of OPSCCs unrelated to HPV.
Topics: Biomarkers, Tumor; Carcinoma, Squamous Cell; Cyclin-Dependent Kinase Inhibitor p16; Epstein-Barr Virus Infections; Female; Herpesvirus 4, Human; Humans; Male; Middle Aged; Oropharyngeal Neoplasms; Papillomaviridae; Papillomavirus Infections; Polyomavirus; Polyomavirus Infections; Prognosis; Tumor Virus Infections
PubMed: 32314041
DOI: 10.1007/s00262-020-02570-3 -
Aging Jul 2020In the context of transplantation with the use of immunosuppressive drugs, BK virus infection has become the main cause of BK virus nephropathy(BKVN) in renal transplant...
In the context of transplantation with the use of immunosuppressive drugs, BK virus infection has become the main cause of BK virus nephropathy(BKVN) in renal transplant recipients(KTRs). More importantly, BKVN may cause further allograft dysfunction and loss. However, the role of the immune microenvironment in the pathogenesis of BKVN remains unknown. Therefore, we collected microarray data of KTRs to elucidate the immune characteristics of BKVN. Via the CIBERSORT, we found that BKVN had relatively more activated memory CD4 T cells. Immunostaining showed that CD4+ and CD8+cells were significantly different between BKVN and stable allografts(STAs). In addition, the expression of immune-related genes(antigen presentation, cytotoxicity, and inflammation) was significantly higher in BKVN than in STAs. The results of gene set enrichment analysis(GSEA) and single-sample GSEA(ssGSEA) indicated that immune cell-,cytokine-,chemokine-, and inflammation-related pathways were significantly activated in BKVN, while metabolism- and renal development-related pathways were significantly downregulated in BKVN. In addition, the immune microenvironments of the peripheral blood in patients with BK viremia(BKV) or transplant kidney biopsy(TKB) with BKVN may be different. Overall, the immune microenvironment may play important roles in the occurrence and development of BKVN and provide a theoretical basis for preventing the occurrence of BKVN and finding novel treatments.
Topics: Adult; BK Virus; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Cellular Microenvironment; Chemokines; Cytokines; Female; Gene Expression Regulation; Humans; Inflammation; Kidney; Kidney Diseases; Kidney Transplantation; Male; Microarray Analysis; Polyomavirus Infections; Signal Transduction; Transplant Recipients
PubMed: 32668411
DOI: 10.18632/aging.103486 -
Brain, Behavior, & Immunity - Health Aug 2021Progressive multifocal leukoencephalopathy (PML) is a rare demyelinating disease of the white matter central nervous system occurring in immunocompromised patients...
Progressive multifocal leukoencephalopathy (PML) is a rare demyelinating disease of the white matter central nervous system occurring in immunocompromised patients particularly those with T cell deficiency such as in HIV, haematological and solid organ malignancies and those taking immunomodulatory medications. PML is caused by JC virus however in rare cases BK virus has been isolated in the cerebral spinal fluid of patients presenting with PML. In this case we describe a 49 year old man who presented to the emergency department with a 2 week history of progressive right sided weakness and dysarthria. His background history included HIV diagnosed in 2005, he had not engaged with care in the past 2 years and had not been taking anti-retroviral therapy (ART). Other past medical history included untreated hepatitis C. His CD4 count was 90 (11%) cells/mm on admission and his HIV viral load VL) was 141,000 copies/ml. Magnetic resonance imaging(MRI) showed a hypointense lesion on T1, hyperintense on T2 and FLAIR without diffusion restriction and without mass effect. A lumbar puncture was performed which confirmed JC virus was positive (PCR <50 copies/ml) and also revealed BK virus was positive (PCR 46,511 copies/ml). The patient was commenced on tenofovir alafenamide fumarate/emtricitabine/darunavir/cobicistat in combination with dolutegravir 50mg twice daily. On day 40 post commencement of ART the patient was readmitted with worsening of his right arm weakness and dysarthria. A repeat MRI was performed which showed the hyperdense lesion on T2 and FLAIR appeared slightly larger with some slight enhancement with gadolinium contrast but no other features suggesting PML immune reconstitution inflammatory syndrome (IRIS). The CD4 count had increased to 141(17%) and HIV VL had decreased to 85 copies/ml. A clinical diagnosis of PML IRIS was made and the patient was commenced on prednisolone 30mg BD which lead to an initial improvement in symptoms. Interestingly in this case, both JC virus and BK virus were detected in the CSF of this patient with the level of JC virus being too low to quantify. BK virus was not detectable on peripheral serum sampling suggesting that BK virus is replicating in the CNS independent of other body sites. There have been 5 case reports in the literature of BK virus as the cause of PML. Testing for BK virus should be considered in patients presenting with signs and symptoms of PML and encephalitis particularly when no other cause is found.
PubMed: 34589769
DOI: 10.1016/j.bbih.2021.100263 -
Cureus Jan 2023BK polyomavirus has been well-studied as an opportunistic infection in immunocompromised kidney transplant patients. In the majority of the population, BK polyomavirus...
BK polyomavirus has been well-studied as an opportunistic infection in immunocompromised kidney transplant patients. In the majority of the population, BK polyomavirus establishes a lifelong infection in renal tubular and uroepithelial cells; however, in an immunocompromised state, the virus can reactivate and can lead to BK polyomavirus-associated nephropathy (BKN). In this case, the patient was a 46-year-old male with a past medical history of HIV, compliant with antiretroviral therapy (ART), and B-cell lymphoma treated with chemotherapy. The patient presented with worsening kidney function of unknown etiology. This prompted further assessment with a kidney biopsy. Kidney biopsy findings were consistent with BKN. In the literature, BKN has been studied in renal transplant patients; however, it rarely involves native kidneys.
PubMed: 36874648
DOI: 10.7759/cureus.34410 -
Intercellular Transmission of Naked Viruses through Extracellular Vesicles: Focus on Polyomaviruses.Viruses Sep 2020Extracellular vesicles have recently emerged as a novel mode of viral transmission exploited by naked viruses to exit host cells through a nonlytic pathway.... (Review)
Review
Extracellular vesicles have recently emerged as a novel mode of viral transmission exploited by naked viruses to exit host cells through a nonlytic pathway. Extracellular vesicles can allow multiple viral particles to collectively traffic in and out of cells, thus enhancing the viral fitness and diversifying the transmission routes while evading the immune system. This has been shown for several RNA viruses that belong to the Picornaviridae, Hepeviridae, Reoviridae, and Caliciviridae families; however, recent studies also demonstrated that the BK and JC viruses, two DNA viruses that belong to the Polyomaviridae family, use a similar strategy. In this review, we provide an update on recent advances in understanding the mechanisms used by naked viruses to hijack extracellular vesicles, and we discuss the implications for the biology of polyomaviruses.
Topics: Antibodies, Neutralizing; Antibodies, Viral; Endocytosis; Extracellular Vesicles; Humans; Immune Evasion; Polyomavirus; Polyomavirus Infections; Tumor Virus Infections; Virus Internalization; Virus Replication
PubMed: 32993049
DOI: 10.3390/v12101086 -
Kidney International Jul 2022Kidney transplant injury processes are associated with molecular changes in kidney tissue, primarily related to immune cell activation and infiltration. How these...
Kidney transplant injury processes are associated with molecular changes in kidney tissue, primarily related to immune cell activation and infiltration. How these processes are reflected in the circulating immune cells, whose activation is targeted by strong immunosuppressants, is poorly understood. To study this, we analyzed the molecular alterations in 384 peripheral blood samples from four European transplant centers, taken at the time of a kidney allograft biopsy, selected for their phenotype, using RNA-sequencing. In peripheral blood, differentially expressed genes in 136 rejection and 248 no rejection samples demonstrated upregulation of glucocorticoid receptor and nucleotide oligomerization domain-like receptor signaling pathways. Pathways enriched in antibody-mediated rejection (ABMR) were strongly immune-specific, whereas pathways enriched in T cell-mediated rejection were less immune related. In polyomavirus infection, upregulation of mitochondrial dysfunction and interferon signaling pathways was seen. Next, we integrated the blood results with transcriptomics of 224 kidney allograft biopsies which showed consistently upregulated genes per phenotype in both blood and biopsy. In single-cell RNASeq (scRNASeq) analysis of seven kidney allograft biopsies, the consistently overexpressed genes in ABMR were mostly expressed by infiltrating leukocytes in the allograft. Similarly, in peripheral blood scRNASeq analysis, these genes were overexpressed in ABMR in immune cell subtypes. Furthermore, overexpression of these genes in ABMR was confirmed in independent cohorts in blood and biopsy. Thus, our results highlight the immune activation pathways in peripheral blood leukocytes at the time of kidney allograft pathology, despite the use of current strong immunosuppressants, and provide a framework for future therapeutic interventions.
Topics: Allografts; Antibodies; Biopsy; Graft Rejection; Immunosuppressive Agents; Kidney; Kidney Transplantation; Transcriptome
PubMed: 35526671
DOI: 10.1016/j.kint.2022.03.026 -
Viruses Feb 2024Microcirculatory and coagulation disturbances commonly occur as pathological manifestations of systemic viral infections. Research exploring the role of the... (Review)
Review
Microcirculatory and coagulation disturbances commonly occur as pathological manifestations of systemic viral infections. Research exploring the role of the kallikrein-kinin system (KKS) in flavivirus infections has recently linked microvascular dysfunctions to bradykinin (BK)-induced signaling of B2R, a G protein-coupled receptor (GPCR) constitutively expressed by endothelial cells. The relevance of KKS activation as an innate response to viral infections has gained increasing attention, particularly after the reports regarding thrombogenic events during COVID-19. BK receptor (B2R and B1R) signal transduction results in vascular permeability, edema formation, angiogenesis, and pain. Recent findings unveiling the role of KKS in viral pathogenesis include evidence of increased activation of KKS with elevated levels of BK and its metabolites in both intravascular and tissue milieu, as well as reports demonstrating that virus replication stimulates BKR expression. In this review, we will discuss the mechanisms triggered by virus replication and by virus-induced inflammatory responses that may stimulate KKS. We also explore how KKS activation and BK signaling may impact virus pathogenesis and further discuss the potential therapeutic application of BKR antagonists in the treatment of hemorrhagic and respiratory diseases.
Topics: Humans; Kallikrein-Kinin System; Endothelial Cells; Microcirculation; Bradykinin; COVID-19
PubMed: 38400022
DOI: 10.3390/v16020245