scholarly journals BK Virus RNA in Renal Allograft Biopsies

2020 ◽  
Vol 68 (5) ◽  
pp. 319-325 ◽  
Author(s):  
Francesca Costigliolo ◽  
Kara Lombardo ◽  
Lois J. Arend ◽  
Avi Z. Rosenberg ◽  
Andres Matoso ◽  
...  
Keyword(s):  
Renal Allograft ◽  
Jc Virus ◽  
Graft Loss ◽  
T Antigen ◽  
Bk Virus ◽  
Kidney Transplant Recipients ◽  
Sv40 Large T Antigen ◽  
Virus Rna ◽  
Allograft Biopsy ◽  
Alternative Test

BK polyomavirus–associated nephropathy (BKpyVAN) remains a cause of graft loss in kidney transplant recipients on immunosuppressive therapy. Its diagnosis relies on the identification of BK virus (BKV) in the renal allograft biopsy by positive immunohistochemical (IHC) stain for the viral SV40 large T antigen, although in situ hybridization (ISH) for viral DNA is used in some centers. We examined tissue detection of BKV RNA by RNAscope, a novel, automated ISH test, in 61 allograft biopsies from 56 patients with BKpyVAN. We found good correlation between the estimate of BKV tissue load by RNAscope ISH and SV40 IHC ( R2 = 0.65, p<0.0001). RNAscope ISH showed 88% sensitivity and 79% specificity and, as an alternative test, could confirm the presence of BKV tissue in presumed BKpyVAN and rule out BKV as the causative agent in JC virus nephropathy. We also used tissue BK viral load estimates by both RNAscope ISH and SV40 IHC to examine the relation between tissue and plasma BK levels and found significant correlation only between BK viremia and tissue BK measured by RNAscope ISH. Our findings suggest that the RNAscope ISH assay could be a reliable test for BKV detection in allograft biopsies.

scholarly journals BK Virus Replication in the Glomerular Vascular Unit: Implications for BK Virus Associated Nephropathy

Viruses ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 583 ◽  
Author(s):  
Waldemar Popik ◽  
Atanu K. Khatua ◽  
Noyna F. Fabre ◽  
James E. K. Hildreth ◽  
Donald J. Alcendor
Keyword(s):  
Endothelial Cells ◽  
Mesangial Cells ◽  
Graft Loss ◽  
T Antigen ◽  
Bk Virus ◽  
Positive Staining ◽  
Sv40 Large T Antigen ◽  
Qrt Pcr ◽  
Transplant Patients ◽  
Glomerular Endothelial Cells

Background: BK polyomavirus (BKV) reactivates from latency after immunosuppression in renal transplant patients, resulting in BKV-associated nephropathy (BKVAN). BKVAN has emerged as an important cause of graft dysfunction and graft loss among transplant patients. BKV infection in kidney transplant patients has increased over recent decades which correlates with the use of more potent immunosuppressive therapies. BKV infection of the Glomerular Vascular Unit (GVU) consisting of podocytes, mesangial cells, and glomerular endothelial cells could lead to glomerular inflammation and contribute to renal fibrosis. The effects of BKV on GVU infectivity have not been reported. methods: We infected GVU cells with the Dunlop strain of BKV. Viral infectivity was analyzed by microscopy, immunofluorescence, Western blot analysis, and quantitative RT-PCR (qRT-PCR). The expression of specific proinflammatory cytokines induced by BKV was analyzed by qRT-PCR. Results: BKV infection of podocytes, mesangial cells, and glomerular endothelial cells was confirmed by qRT-PCR and positive staining with antibodies to the BKV VP1 major capsid protein, or the SV40 Large T-Antigen. The increased transcriptional expression of interferon gamma-induced protein 10 (CXCL10/IP-10) and interferon beta (IFNβ) was detected in podocytes and mesangial cells at 96 h post-infection. conclusions: All cellular components of the GVU are permissive for BKV replication. Cytopathic effects induced by BKV in podocytes and glomerular endothelial cells and the expression of CXCL10 and IFNβ genes by podocytes and mesangial cells may together contribute to glomerular inflammation and cytopathology in BKVAN.

scholarly journals Regulation of Gene Expression in Primate Polyomaviruses

2009 ◽  
Vol 83 (21) ◽  
pp. 10846-10856 ◽  
Author(s):  
Martyn K. White ◽  
Mahmut Safak ◽  
Kamel Khalili
Keyword(s):  
Gene Expression ◽  
Jc Virus ◽  
Regulation Of Gene Expression ◽  
T Antigen ◽  
Bk Virus ◽  
Viral Gene ◽  
Cell Type ◽  
Cell Type Specificity ◽  
Karolinska Institute ◽  
Human Polyomaviruses

ABSTRACT Polyomaviruses are a growing family of small DNA viruses with a narrow tropism for both the host species and the cell type in which they productively replicate. Species host range may be constrained by requirements for precise molecular interactions between the viral T antigen, host replication proteins, including DNA polymerase, and the viral origin of replication, which are required for viral DNA replication. Cell type specificity involves, at least in part, transcription factors that are necessary for viral gene expression and restricted in their tissue distribution. In the case of the human polyomaviruses, BK virus (BKV) replication occurs in the tubular epithelial cells of the kidney, causing nephropathy in kidney allograft recipients, while JC virus (JCV) replication occurs in the glial cells of the central nervous system, where it causes progressive multifocal leukoencephalopathy. Three new human polyomaviruses have recently been discovered: MCV was found in Merkel cell carcinoma samples, while Karolinska Institute Virus and Washington University Virus were isolated from the respiratory tract. We discuss control mechanisms for gene expression in primate polyomaviruses, including simian vacuolating virus 40, BKV, and JCV. These mechanisms include not only modulation of promoter activities by transcription factor binding but also enhancer rearrangements, restriction of DNA methylation, alternate early mRNA splicing, cis-acting elements in the late mRNA leader sequence, and the production of viral microRNA.

Detection of CD8+ T Cells Sensitized to BK Virus Large T Antigen in Healthy Volunteers and Kidney Transplant Recipients

2006 ◽  
Vol 67 (4-5) ◽  
pp. 298-302 ◽  
Author(s):  
Parmjeet S. Randhawa ◽  
Iulia Popescu ◽  
Camila Macedo ◽  
Adriana Zeevi ◽  
Ron Shapiro ◽  
...  
Keyword(s):  
T Cells ◽  
Healthy Volunteers ◽  
Kidney Transplant ◽  
Cd8 T Cells ◽  
T Antigen ◽  
Bk Virus ◽  
Large T Antigen ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients

scholarly journals T-cell responses to peptide fragments of the BK virus T antigen: implications for cross-reactivity of immune response to JC virus

2006 ◽  
Vol 87 (10) ◽  
pp. 2951-2960 ◽  
Author(s):  
Jongming Li ◽  
Jos Melenhorst ◽  
Nancy Hensel ◽  
Katyoun Rezvani ◽  
Giuseppe Sconocchia ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Jc Virus ◽  
Sequence Similarity ◽  
Simian Virus 40 ◽  
T Cell Responses ◽  
T Antigen ◽  
Bk Virus ◽  
Cell Responses ◽  
Cross Immunity

Infection with BK virus (BKV) induces both humoral and cellular immunity, but the viral antigens of T-antigen (T-ag) stimulating T-cell responses are largely unknown. To identify BKV-specific T cells in healthy individuals, peripheral blood lymphocytes were cultured with autologous dendritic cells (DCs) loaded with BKV lysate and T cells were screened for intracellular gamma interferon production after stimulation with an overlapping 15mer peptide library of the BKV T-ag. Among many immunogenic peptides identified, four T-ag peptides were identified as candidate major histocompatibility complex class I and II T-cell epitopes, restricted to human leukocyte antigen (HLA)-B*0702, -B*08, -DRB1*0301 and -DRB1*0901. Further, a candidate 9mer peptide, LPLMRKAYL, was confirmed to be restricted to HLA-B*0702 and -B*08. Because the polyomaviruses BKV, JC virus (JCV) and Simian virus 40 (SV40) share extensive sequence similarity in the immunogenic proteins T-ag and VP1, it was hypothesized that, in humans, these proteins contain conserved cytotoxic T-lymphocyte (CTL) target epitopes. Four HLA-restricted conserved epitopes of BKV, JCV and SV40 were identified: HLA-B*07, -B*08 and -DRB1*0901 for T-ag and -A*0201 for VP1. T cells cultured in vitro that were specific for one viral antigen recognized other conserved epitopes. CTLs generated from BKV T-ag and VP1 peptide were cytotoxic to DC targets pulsed with either BKV or JCV. Therefore, infection by one of the two viruses (BKV and JCV) could establish cross-immunity against the other. Although cross-cytotoxicity experiments were not performed with SV40, cross-recognition data from conserved antigen epitopes of polyomaviruses suggest strongly that cross-immunity might also exist among the three viruses.

scholarly journals Potential Transmission of Human Polyomaviruses through the Gastrointestinal Tract after Exposure to Virions or Viral DNA

2001 ◽  
Vol 75 (21) ◽  
pp. 10290-10299 ◽  
Author(s):  
Sı́lvia Bofill-Mas ◽  
Meritxell Formiga-Cruz ◽  
Pilar Clemente-Casares ◽  
Francesc Calafell ◽  
Rosina Girones
Keyword(s):  
Jc Virus ◽  
Regulatory Region ◽  
The United States ◽  
T Antigen ◽  
Bk Virus ◽  
Virus Concentration ◽  
Viral Dna ◽  
Viral Particles ◽  
The Stability ◽  
Time Required

ABSTRACT The mechanism of human-to-human transmission of the polyomaviruses JC virus (JCV) and BK virus (BKV) has not been firmly established with regard to possible human exposure. JCV and BKV have been found in sewage samples from different geographical areas in Europe, Africa, and the United States, with average concentrations of 102 to 103 JCV particles/ml and 101 to 102BKV particles/ml. Selected polyomavirus-positive sewage samples were further characterized. The JCV and BKV present in these samples were identified by sequencing of the intergenic region (the region found between the T antigen and VP coding regions) of JCV and the VP1 region of BKV. The regulatory region of the JCV and BKV strains found in sewage samples presented archetypal or archetype-like genetic structures, as described for urine samples. The stability (the time required for a 90% reduction in the virus concentration) of the viral particles in sewage at 20°C was estimated to be 26.7 days for JCV and 53.6 days for BKV. The presence of JCV in 50% of the shellfish samples analyzed confirmed the stability of these viral particles in the environment. BKV and JCV particles were also found to be stable at pH 5; however, treatment at a pH lower than 3 resulted in the detection of free viral DNA. Since most humans are infected with JCV and BKV, these data indicate that the ingestion of contaminated water or food could represent a possible portal of entrance of these viruses or polyomavirus DNA into the human population.

scholarly journals A Review on JC Virus Infection in Kidney Transplant Recipients

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Serena Delbue ◽  
Mariano Ferraresso ◽  
Luciana Ghio ◽  
Camilla Carloni ◽  
Silvia Carluccio ◽  
...  
Keyword(s):  
Renal Transplantation ◽  
Demyelinating Disease ◽  
Jc Virus ◽  
Graft Function ◽  
Kidney Tissue ◽  
Bk Virus ◽  
Pathological Features ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Dna Virus

The polyomavirus (PyV), JC virus (JCV), is a small nonenveloped DNA virus that asymptomatically infects about 80% of healthy adults and establishes latency in the kidney tissue. In case of immunodeficient hosts, JCV can lytically infect the oligodendrocytes, causing a fatal demyelinating disease, known as progressive multifocal leukoencephalopathy (PML). Although the reactivation of another human PyV, BK virus (BKV), is relatively common and its association with the polyomavirus associated nephropathy (PyVAN) following renal transplantation is proven, JCV replication and its impact on graft function and survival are less well studied. Here we describe the biology of JCV and its pathological features and we review the literature regarding the JCV infection analyzed in the setting of transplantations.

scholarly journals Induction Immunosuppression in Pediatric Kidney Transplant Recipients Under the Age of 11 with Rabbit Anti-Thymocyte Globulin

2020 ◽  
Vol 3 ◽  
Author(s):  
William Goggins ◽  
Richard Mangus ◽  
Burcin Ekser ◽  
William Goggins
Keyword(s):  
Kidney Transplant ◽  
Graft Survival ◽  
Lymphoproliferative Disorder ◽  
Graft Loss ◽  
Bk Virus ◽  
P Value ◽  
Induction Agent ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Post Transplant

Background:     At the time of kidney transplantation (KT), induction immunosuppression is used to reduce the incidence of early rejection and avoid the use of chronic corticosteroids in maintenance immunosuppression. There is currently no standard of care for induction immunosuppression in the pediatric recipient, instead it is based on institutional preference. In this study, we compare our current induction immunosuppression, rabbit anti-thymocyte globulin (rATG), to our previous induction immunosuppression, Daclizumab in patients under the age of 11.     Methods:     From 07/2004 to 08/2019, 79 patients under the age of 11 have received a KT. 7 patients were excluded from analysis due to Basiliximab induction (n=3), graft loss within 10 days (n=3) and patient death (n=1). 72 patients were analyzed, of which 39 patients (54%) with rATG induction were compared to 33 patients (46%) with daclizumab induction. All patients were maintained on steroid-free immunosuppression regimen after transplant. More than 20 variables were followed, along with rejection, graft failure, and any prevalence of post-transplant lymphoproliferative disorder (PTLD) was recorded (Figure 1).    Results:     Patients demographics were similar in both groups. Graft survival was good and statistically similar up to 5 years. In both groups, serum creatinine levels were similar up to 1 year follow up. Although CMV infection was similar in both groups, BK viremia and BK virus in the urine were more frequent in rATG group. Post-transplant lymphoproliferative disorder was significantly higher in the Daclizumab group (p=0.022), but less acute rejection was observed in the Daclizumab group (Figure 1).     Potential Impact:     Our study suggests that rATG is a safe and effective induction agent in pediatric kidney transplant recipients under the age of 11. Recipients have excellent patient and graft survival. It is associated with strong kidney function and low PTLD. Screening for BK virus in the urine is essential with rATG induction.     Table 1:     Induction Agent  Daclizumab  rATG  p value  Demographics        Number  33  39  N.S.  Sex  15M, 18F  27M, 12F  0.042  Age (years)  5.5 ± 2.7  6.1 ± 2.7  N.S.  Height (m)  1.02 ± 0.23  1.06 ± .21  N.S.  Weight (kg)  18.75 ± 9.93  19.08 ± 6.42  N.S.  Outcomes        Cr 1 month (mg/dL)  0.56 ± .31  0.45 ± .17  0.056  Cr 6 months (mg/dL)  0.54 ± .22  0.52 ± .18  N.S.  Cr 1 year (mg/dL)  0.63 ± .27  0.59 ± .17  N.S.  eGFR 1 month (ml/min/1.73m2)  84.81 ± 27.95  107.08 ± 30.09  0.0019  eGFR 6 months (ml/min/1.73m2)  85.04 ± 27.60  92.48 ± 28.07  N.S.  eGFR 1 year (ml/min/1.73m2)  74.31 ± 26.8  79.3 ± 22.01  N.S.  Rejection 6 months  1 (3.03%)  8 (20.51%)  0.0188  Rejection 1 year  2 (6.06%)  8 (20.51%)  0.0682  Graft Survival 1 year  100% (33/33)  100% (39/39)  N.S.  Graft Survival 3 years  96.97% (32/33)  100% (25/25)  N.S.  Graft Survival 5 years  96.88 (31/32)  100% (22/22)  N.S.  Cases of PTLD  5 (18.18%)  0 (0%)  0.022  Chronic steroid use  2 (6.06%)  2 (5.13%)  N.S.  BK Urine only 1 year  0% (0/33)*  10.26% (4/39)  0.0439  BK Viremia 1 year  3.03% (1/33)*  17.95% (7/39)  0.0356  CMV Viremia 1 year  0% (0/33)  5.13% (2/39)  N.S.  N.S.= Not statistically significant.  *BK screening was not routine during time of daclizumab induction 

scholarly journals Immunoglobulin G, A, and M Responses to BK Virus in Renal Transplantation

2006 ◽  
Vol 13 (9) ◽  
pp. 1057-1063 ◽  
Author(s):  
Parmjeet S. Randhawa ◽  
Gaurav Gupta ◽  
Abhay Vats ◽  
Ron Shapiro ◽  
Raphael P. Viscidi
Keyword(s):  
Viral Replication ◽  
Optical Density ◽  
Immunoglobulin G ◽  
Jc Virus ◽  
Bk Virus ◽  
Enzyme Linked Immunosorbent Assay ◽  
Kidney Transplant Recipients ◽  
Serum Samples ◽  
Igm Antibodies ◽  
Active Viral Replication

ABSTRACT Immunoglobulin G (IgG), IgA, and IgM antibodies were measured in serum samples from 71 organ donors, 81 kidney transplant recipients at transplantation, and 67 patients during the posttransplant period by using a virus-like particle-based enzyme-linked immunosorbent assay (ELISA). BK virus (BKV) and JC virus DNA were detected in urine and plasma by real-time PCR. IgG antibodies to BKV were demonstrated in the majority (80.3 to 100%) of patients irrespective of clinical category, but titers were highest in patients with active viral replication. IgA antibodies were present with greater frequency (72.7 to 81.3% versus 0 to 23.6%; P < 0.001) and higher titer (mean optical density, 0.11 to 0.15 versus 0.05 to 0.08; P < 0.001) in patients who were BKV DNA positive than those who were BKV DNA negative. IgM antibodies showed a similar pattern of reactivity but lower frequency in the setting of active viral replication (9.1 to 43.7% versus 0 to 1.4%; P < 0.001). A rise in IgG level of >0.577 optical density (OD) units or a rise in IgA or IgM level of >0.041 OD units was strongly associated with active viral replication. Urine viral load showed a positive correlation with IgM titer (r = 0.22) but a negative correlation with IgG titer (r = −0.28) and IgA titer (r = −0.1). Chronic dialysis patients typically did not have serologic or virologic evidence of active BKV infection. Anti-BKV titers did not rise in patients with JC viruria. In conclusion, measurement of anti-BKV antibody titer and class response can be used to detect the onset of viral replication. ELISAs can be quite specific despite considerable sequence homology between BK virus and JC virus.

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