BK polyomavirus subtype III in a pediatric renal transplant patient with nephropathy.
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ABSTRACT:
SUBMITTER: Kapusinszky B
PROVIDER: S-EPMC3838085 | biostudies-literature | 2013 Dec
REPOSITORIES: biostudies-literature
Publications
BK polyomavirus subtype III in a pediatric renal transplant patient with nephropathy.
Kapusinszky Beatrix B Chen Sharon F SF Sahoo Malaya K MK Lefterova Martina I MI Kjelson Lynn L Grimm Paul C PC Kambham Neeraja N Concepcion Waldo W Pinsky Benjamin A BA
Journal of clinical microbiology 20130918 12
BK polyomavirus (BKV) is an emerging pathogen in immunocompromised individuals. BKV subtype III is rarely identified and has not previously been associated with disease. Here we provide the whole-genome sequence of a subtype III BKV from a pediatric kidney transplant patient with polyomavirus-associated nephropathy. ...[more]
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Project description:We report here the complete genome sequence of polyomavirus BK subtype Ib-1, isolate AR11, identified in urine from a human kidney transplant recipient with a clinical diagnosis of BK viremia. The AR11 isolate is closely related to reference strain human polyomavirus 1 isolate J2B-2 with 99% identity.
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Project description:BackgroundThe immunosuppressive agents mycophenolate acid (MPA) and tacrolimus (Tac) are associated with a higher incidence of BK polyomavirus nephropathy (BKPyVAN). In this observational retrospective cohort study, the frequency of BK polyomavirus (BKPyV) complications over a 24-month period was studied.Methods358 renal transplant recipients (RTR) treated with MPA, with either cyclosporine A (CsA) (CsAM group) or Tac (TacM group) and mostly prednisolone, were included.ResultsIncidence of BKPyV-viremia was not significantly different between the CsAM (n = 42/191) (22.0%) and the TacM (n = 36/167) (21.6%) group. Biopsy proven BKPyVAN occurred more often in the TacM group (6.6%) versus the CsAM group (2.1%) (p = 0.03). Longitudinal data analysis showed a significant earlier decline of viral load in plasma in the CsAM group compared to the TacM group (p = 0.005). The incidence of biopsy proven acute rejection (BPAR) was significantly higher in the CsAM (19.9%) compared to the TacM (10.8%) (p = 0.02) group. Graft loss, estimated glomerular filtration rate and mortality rate did not differ in both treatment groups.ConclusionIn conclusion, this study shows that immunosuppressive treatment with Tac and MPA compared to CsA and MPA is associated with a lower incidence of BPAR, but at the cost of an increased risk of developing BKPyVAN in the first two years post-transplant.
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Project description:ObjectiveThis study aimed to explore the molecular mechanism of cytoplasmic vacuolation caused by BK polyomavirus (BKPyV) and thus search for potential target for drug repurposing.MethodsMorphological features of BK polyomavirus-associated nephropathy (BKPyVAN) were studied under light and electron microscopes. Microarray datasets GSE75693, GSE47199, and GSE72925 were integrated by ComBat, and differentially expressed genes (DEGs) were analyzed using limma. Furthermore, the endoplasmic reticulum (ER)-related genes obtained from GenCLiP 2.0 were intersected with DEGs. GO and KEGG enrichment pathways were performed with intersection genes by R package clusterProfiler. The single-cell RNA sequencing (scRNA-seq) from a BKPyVAN recipient was analyzed with a dataset (GSE140989) downloaded from Gene Expression Omnibus (GEO) as control for gene set variation analysis (GSVA). Immunohistochemistry and electron microscopy of kidney sections from drug-induced ERS mouse models were performed to explore the association of ERS and renal tubular vacuolation. Protein-protein interaction (PPI) network of the intersection genes was constructed to identify hub target. AutoDock was used to screen Food and Drug Administration (FDA)-approved drugs that potentially targeted hub gene.ResultsLight and electron microscopes exhibited obvious intranuclear inclusions, vacuoles, and virus particles in BKPyV-infected renal tubular cells. Transcriptome analysis revealed 629 DEGs between samples of BKPyVAN and stable transplanted kidneys, of which 16 were ER-associated genes. GO analysis with the intersection genes illustrated that ERS-related pathways were significantly involved, and KEGG analysis showed a prominent enrichment of MAPK, Toll-like receptor, and chemokine signaling pathways. GSVA analysis of the proximal tubule revealed similar pathways enrichment. An electron microscope image of the kidney from ERS mouse models showed an obvious renal tubular vacuolation with prominent activation of ERS markers verified by immunohistochemistry. Furthermore, DDIT3 was identified as the hub gene based on PPI analysis, and ZINCOOOOO1531009 (Risedronate) was indicated to be a potential drug for DDIT3.ConclusionERS was involved in renal tubular cytoplasmic vacuolation in BKPyVAN recipients. Risedronate was screened as a potential drug for BKPyVAN by targeting DDIT3.
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Project description:We report here the nearly complete genome sequences of two human BK polyomavirus (BKV) strains recovered from two Vietnamese renal allograft recipients and belonging to subtypes IVc1 (strain VN_PBK185) and Ib1 (strain VN_PBK212). The genome sequences of VN_PBK185 and VN_PBK212 were highly similar (99.9% nucleotide identity) to the reference BKV strains VNM-1 and VNM-9, respectively.
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Project description:BK polyomavirus nephropathy (BKVN) and allograft rejection are two closely-associated diseases on opposite ends of the immune scale in kidney transplant recipients. The principle of balancing the immune system remains the mainstay of therapeutic strategy. While patient outcomes can be improved through screening, risk factors identification, and rapid reduction of immunosuppressants, a lack of standard curative therapy is the primary concern during clinical practice. Additionally, difficulty in pathological differential diagnosis and clinicopathology's dissociation pose problems for a definite diagnosis. This article discusses the delicate evaluation needed to optimize immunosuppression and reviews recent advances in molecular diagnosis and immunological therapy for BKVN patients. New biomarkers for BKVN diagnosis are under development. For example, measurement of virus-specific T cell level may play a role in steering immunosuppressants. The development of cellular therapy may provide prevention, even a cure, for BKVN, a complex post-transplant complication.
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Project description:BackgroundAlthough early monitoring of BK virus infection in renal transplant patients has led to improved outcomes over the past decade, it remains unclear whether monitoring for viremia is the best screening tool for BK virus nephropathy (BKVN).MethodsWe conducted a retrospective review of the medical records of 368 renal transplant recipients who had a minimum of 18 months of posttransplantation follow-up. The relationship between the presence of BK viruria and a composite end point of BK viremia/BKVN was established, and the predictive value of high-grade BK viruria for development of viremia/BKVN was determined.ResultsHigh grade of BK viruria was present in 110 (30.1%) of the renal transplant recipients. BK viremia/BKVN was present in 64 (17.4%) patients and was 50 times more likely to be present in patients with high-grade BK viruria. The risk of developing BK viremia/BKVN was 3 times higher in high-grade viruria patients, and viruria preceded viremia by nearly 7 weeks.ConclusionThe presence of high-grade viruria is an early marker for developing BK viremia/BKVN. Detection of high-grade viruria should prompt early allograft biopsy and/or preemptive reduction in immunosuppression.
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