BK Polyomavirus Infection Research Articles

Host cell autophagy promotes BK virus infection

Autophagy is important for a variety for virus life cycles. We sought to determine the role of autophagy in human BK polyomavirus (BKPyV) infection. The addition excess amino acids during viral infection reduced BKPyV infection. Perturbing autophagy levels using inhibitors, 3-MA, bafilomycin A1, and spautin-1, also reduced infection, while rapamycin treatment of host cells increased infection. siRNA knockdown of autophagy genes, ATG7 and Beclin-1, corresponded to a decrease in BKPyV infection. BKPyV infection not only correlated with autophagosome formation, but also virus particles localized to autophagy-specific compartments early in infection. These data support a novel role for autophagy in the promotion of BKPyV infection.

(319) - Prevalence of BK Polyomavirus Infection and Association with Renal Function in Pediatric Heart Transplant Recipients

(319) - Prevalence of BK Polyomavirus Infection and Association with Renal Function in Pediatric Heart Transplant Recipients

Association of DNA Amplification With Progress of BK Polyomavirus Infection and Nephropathy in Renal Transplant Recipients

PurposeBK polyomavirus-associated nephropathy (BKVAN) is an important cause of renal allograft loss. Immunosuppression therapy in renal transplant recipients can lead to the reactivation of latent BK polyomavirus (BKV) infection, leading to BK viruria and viremia. This single-center study aimed to clarify the association between quantitative measurement of BKV DNA and the progression of BKV infection, and secondly to identify the risk factors associated with the evolution of viruria to viremia. MethodsWe retrospectively analyzed 266 patients who underwent renal transplantation in our center from October 2006 to February 2013. We examined the viral loads of BKV in urine and plasma by quantitative real-time polymerase chain reaction assay after screening all of the recipients by urinary sediment examination. BKVAN was diagnosed by histological examination with immunohistochemistry of the large T antigen in biopsy specimens. ResultsOverall, 22 recipients showed BK viruria alone, whereas 22 progressed to BK viremia, of which 6 patients were diagnosed with BKVAN. Among BKVAN patients, 2 cases progressed to graft loss at 59 months and 31 months after diagnosis, respectively. In BKVAN group, the plasma viral loads were significantly higher than those in viremia without nephropathy (P < .001). Multivariate analysis revealed that the evolution of viruria to viremia was associated with recipient age over 55 years (odds ratio, 32.08; 95% confidence interval, 2.1–489.5) and tacrolimus exposure (odds ratio, 11.98; 95% confidence interval, 1.34–107.04). ConclusionsThe progression from viremia to BKVAN was strongly associated with increasing plasma viral loads for BKV DNA. The cutoff value of 1 × 104 copies/mL for plasma viral loads could differentiate between BKVAN and viremia alone. Further, recipient age over 55 years and tacrolimus exposure were independently associated with the evolution of viruria to viremia.

Urinary cytopathologic findings in renal allograft recipients in Sudan: Trends, outcome and challenges

Urine cytology allows frequent monitoring of the intragraft events in renal transplantation and detection of infections associated with renal transplantation as a result of immunosuppression, specifically BK polyoma virus (Decoy cells). We conducted a cross-sectional study aimed to demonstrate the urinary cytomorphological changes among renal allograft recipients. We studied urine samples from 182 renal adult allograft recipients. All grafts were obtained from live donors. All the study population was under immunosuppressive drugs (Cyclosporine, Tacrolimus or azathioprine). Fourteen samples (7.6%) were collected during the first three months following transplantation. The slides of the centrifuged precipitates were stained with Papanicolaou and Diff Quick stains. The slides were screened by a cyto-screener and examined by a consultant cytopathologist for the presence of infectious agents and benign and malignant cellular changes. Of the 182 cases, 120 (65.9%) were negative for cytological changes, 45 (24.7%) showed bacterial infection, eight (4.4%) had BK polyoma virus infection (Decoy cells), four (2.2%) had human papilloma virus (HPV) infection (Koilocytosis) (Figure 1), three (1.6%) showed candida and two (1.1%) had cytomegalovirus infection. Renal transplant recipients are at a high risk for developing infections, including opportunistic infections; this is generally attributed to the immunosuppression status and epidemiologic exposure to infections. During the first posttransplantation year, 40–50% of recipients experience at least one infection. Smears consistent with bacterial infections were the most common finding in our study; they revealed polymorphs, macrophages, necrotic debris and background of bacteria. In our study, eight (4.4%) cases were diagnosed to have BK polyoma virus cytological changes (Decoy cells). Human polyoma viruses are members of the Papova virus family, which have a double strand DNA-genome. Recently, BK virus has been recognized as a cause of severe renal allograft dysfunction and potential graft loss, which are characterized by the presence of Decoy cells that were reported to present in 10–19.7% of urine samples from renal transplant (RT) patients.

BK polyomavirus in kidney transplant recipients: screening, monitoring and clinical management.

BK polyomavirus (BKPyV) is a causal agent of nephropathy, ureteral stenosis and hemorrhagic cystitis in kidney transplant recipients, and is considered an important emerging disease in transplantation. Regular screening for BKPyV reactivation mainly during the first 2 years posttransplant, with subsequent pre-emptive reduction of immunosuppression is considered the best option to avoid disease progression, since successful clearance or reduction of viremia is achieved in the vast majority of patients within 6 months. The use of drugs with antiviral properties for patients with persistent viremia has been attempted despite unclear benefits. Clinical manifestations of BKPyV nephropathy, current strategies for diagnosis and monitoring of BKPyV infection, management of immunosuppressive regimen after detection of BKPyV reactivation and the use of antiviral drugs are discussed in this review.

Decoy cells due to polyomavirus BK infection in the urine sediment of a patient with lupus nephritis

Decoy cells due to polyomavirus BK infection in the urine sediment of a patient with lupus nephritis

A Qualitative Seminested PCR Assay as an Alternative to Urine Cytology for BK Polyomavirus Screening after Renal Transplantation

Objective: Polyomavirus-associated nephropathy (PVAN) is a major cause of graft dysfunction after kidney transplantation. Therefore, routine screening for BK polyomavirus (BKV) infection with urine cytology or quantitative PCR-based assays has been recommended. Although less expensive than quantitative tests, qualitative PCR assays are not recommended for screening based on the assumption that their diagnostic accuracy is inferior to urine cytology. However, studies comparing the performance of both methods are scarce. Methods: We compared the accuracy between a qualitative seminested PCR (snPCR) assay and urine cytology for the screening of BKV viruria in 104 renal transplant recipients. Results: The snPCR assay was more sensitive than cytology (100 and 61%, respectively), yielding better negative predictive value (100 vs. 90%). In 7 (39%) of the 18 PVAN cases, BKV infection was detected exclusively by snPCR. Although the specificity of snPCR (63%) was lower than cytology (74%), their positive predictive values were similar (36 vs. 33%, respectively). In ROC curve analysis, the accuracy of snPCR was significantly higher (p = 0.03). Conclusion: This qualitative snPCR assay was more accurate than urine cytology for the detection of BKV viruria in renal transplant patients.

Immunity to Polyomavirus BK Infection: Immune Monitoring to Regulate the Balance between Risk of BKV Nephropathy and Induction of Alloimmunity

Polyomavirus BK-associated nephropathy (PyVAN) is the main infectious cause of allograft damage after kidney transplantation. A number of studies revealed an association between the presence of BKV-specific cellular immunity and BK viral clearance, with patients failing to recover specific T cells progressing to PyVAN. Evolution to allograft dysfunction can be prevented by restoration of BKV-specific immunity through a stepwise reduction of maintenance immunosuppressive drugs. Prospective monitoring of BK viral load and specific immunity, together with B-cell alloimmune surveillance, may allow a targeted modification/reduction of immunosuppression, with the aim of obtaining viral clearance while preventing graft injury due to deposition of de novo donor-specific HLA antibodies and late/chronic antibody-mediated allograft injury. Innovative, immune-based therapies may further contribute to BKV infection prevention and control.

Detection of BK polyomavirus after kidney transplantation: a comparison of urine electron microscopy with plasma polymerase chain reaction

BK polyomavirus (BKV) infection continues to be a significant source of allograft dysfunction in kidney transplant recipients. The optimal screening method to detect BKV remains undetermined. In this retrospective analysis of 347 consecutive kidney transplant recipients, we compare the diagnostic and screening performance of urine electron microscopy (EM) with plasma polymerase chain reaction (PCR) in testing for BKV, using biopsy-proved polyomavirus-associated nephropathy (PVAN) as the gold standard. Sixty-nine of 347 recipients had a positive screening test for BKV infection. Twenty-nine patients underwent biopsy, and 11 were diagnosed with PVAN. Sensitivity rates of urine EM and plasma PCR were 88% and 100%, respectively. Specificity rates of urine EM and plasma PCR were 91% and 78%. There was no statistical difference in the operating characteristics of the two tests. The majority of both plasma PCR and urine EM tests were positive in the six months prior to a diagnostic biopsy confirming PVAN. In those patients who had evidence of BKV infection but did not have PVAN, the percentage of positive screening tests decreased with aggressive lowering of immunosuppression. We conclude that urine EM and plasma PCR both function well in screening for BKV infection and in the diagnosis of PVAN. There is an opportunity to detect viral replication, lower immunosuppression, and to prevent PVAN in this population.

Ciprofloxacin Prophylaxis in Kidney Transplant Recipients Reduces BK Virus Infection at 3 Months But Not at 1 Year

BK polyomavirus (BKV) infection remains a significant cause of nephropathy and graft loss. Fluoroquinolones inhibit BKV replication in vitro, and small studies suggest in vivo benefit. A strategy of fluoroquinolone prophylaxis directed specifically against BKV has not been formally tested against a control group in kidney transplant recipients. We retrospectively compared the impact of a change in antibiotic prophylaxis practice from no BKV prophylaxis (Group 1, n=106, July-December 2009) to BKV prophylaxis with ciprofloxacin 250 mg twice daily for 30 days (Group 2, n=130, January-June 2010) on the rate of BKV infection during the first 12 months after kidney transplantation. Baseline demographics, transplant characteristics, induction immunosuppression, and 1-year incidence of acute rejection were similar between groups. Group 1 had fewer patients on maintenance corticosteroids (65.1% vs. 83.2%, P=0.002). At 3 months, Group 1 had a significantly higher risk of developing BK viremia (0.161 vs. 0.065, P=0.0378) and viruria (0.303 vs. 0.146, P=0.0067) compared with Group 2, but this difference disappeared at 12 months for both viremia (0.297 vs. 0.261, P=0.6061) and viruria (0.437 vs. 0.389, P=0.5363). Adjusting for the difference in steroid use did not change the results. There was a trend toward higher incidence of biopsy-proven BKV nephropathy in Group 1 (4.7% vs. 0.8%, P=0.057). Thirty-day ciprofloxacin prophylaxis in kidney transplant recipients is associated with a lower rate of BKV infection at 3 months but not at 12 months. The long-term effectiveness and optimal duration of fluoroquinolone prophylaxis against BKV infection remain unknown.

BK Polyoma Virus Induces Aberrant Methylation of Host Genome to Promote Epithelial Mesenchymal Transition and Fibrosis

Although most people are infected during early childhood, BK polyoma virus (BKV) reactivates and causes disease primarily in renal transplant patients. BKV is currently the leading cause of graft loss during the first two years after renal transplant. Activation of BKV is associated with inflammation, tissue destruction and progression to fibrosis through a process involving the transformation of epithelial cells in to mesenchymal phenotype. Understanding how BKV causes these changes will help us in better prediction and management of BKV nephropathy. As the primary site of BKV tropism is renal tubular epithelial cells, it needs to device ways to promote the transition and proliferation of these terminally differentiated cells. We hypothesized that BK may activate epigenetic mechanisms to promote these changes by inducing or inhibiting key genes involved in maintaining cellular integrity and stability. DNA CpG methylation is one such epigenetic mechanism which can control gene regulation by causing changes to the DNA which inhibit the accessibility of transcription factors to gene promoters. For our experiments, we have used primary human proximal renal tubular epithelial cells (HPTC) isolated from donor kidneys or procured from ATCC. Cells were infected with BKV for different time points. Real-time expression profiling was done to identify key genes modulated by BKV. Bisulfite conversion and Methylation specific PCR was used to identify specific CpG changes induced by BKV. Sequencing of the bisulfite converted DNA was done to identify the methylation status of entire CpGs islands in the promoters of these genes. Promoter region with specific CpGs was then cloned in pGL3 luciferase reporter vector to specify the role of particular CpGs in regulation and rule out the effect of trans-acting elements. For luciferase assays, CCD1105 KIDtr and HPTC cells were transfected using Lipofectamine- LTX and Plus reagent, infected with BK virus and assayed using Dual luciferase assay. Cell cycle analysis was done using propidium iodide staining and flow cytometry. Infection of renal epithelial cells by BKV caused induction of proinflammatory genes such as Cox-2 and interleukin 1 Beta along with Vimentin which is the marker for epithelial mesenchymal transition. More importantly, it inhibited retinoblastoma (RB1) and E-cadherin (CDH1) genes. We have for the first time identified that BK inhibits these genes by causing hypermethylation of specific CpG islands in their upstream regulatory promoters. These genes are important regulators of cell-cell adhesion (CDH1) and cell cycle (RB1), and their inhibition may lead to loss of adhesion and cell proliferation respectively. Luciferase Reporter assay using cloned RB1 promoter confirmed the involvement of these CpG islands and showed progressive decrease in RB1 promoter activity with increasing BK infection. Our studies also suggest that BKV infection may lead to increased aneuploidy in these cells further contributing to cellular instability and transformation. The changes induced by BKV may ultimately lead to inflammation, cellular proliferation and progression to renal fibrosis and graft loss. Specific CpG methylation patterns induced by BKV may also serve as biomarkers to predict the initiation of BKV nephropathy and help in devising relevant control strategies.

Early BK Polyomavirus (BKV) Reactivation in Donor Kidney Is a Risk Factor for Development of BKV-Associated Nephropathy

The pathogenesis of BK polyomavirus (BKV) infection and associated nephropathy in renal transplant recipients is not clearly understood. To gain insight, urine and plasma samples were collected from 112 renal transplant recipients before and after transplantation and tested for the presence of BKV by polymerase chain reaction. Detection of BKV infection very early (ie, 5 days) after transplantation was identified as a risk factor for subsequent BKV viremia and BKV-associated nephropathy. Phylogenetic analysis of VP1 sequences with corresponding ethnicity data suggests that reactivation was of donor origin. Thus, early testing of urine samples from renal transplant recipients may identify those at risk for BKV-associated nephropathy.

Risk factors and interventional strategies for BK polyomavirus infection after renal transplantation

BK virus (BKV)-induced viraemia after renal transplantation can be associated with severe impairment of graft function. This study evaluated possible risk factors for BKV replication and examined the outcomes following various currently used treatment approaches. Fifty-seven renal transplant recipients with BKV viraemia were retrospectively compared with 71 BKV-negative recipients to identify risk factors for BKV viraemia. Furthermore, outcome and graft function in 14 patients with BKV replication, in whom mycophenolate mofetil (MMF) was discontinued with a dose reduction of the remaining immunosuppressants, were compared with 32 patients in whom both MMF and the additional immunosuppressants were reduced. Patients with BKV viraemia received MMF (p < 0.01) and triple immunosuppression (p < 0.01) significantly more often, and displayed tacrolimus (p = 0.034) at higher blood concentrations (p = 0.002), a lower lymphocyte count (p = 0.006) and a longer warm ischaemic time (p = 0.019), and were more often male (p = 0.026). Patients in whom MMF was stopped had a higher chance of clearance of BKV viraemia (p = 0.022), which was achieved more rapidly (p = 0.048). Graft function improved during treatment and no graft losses occurred, compared with eight graft losses in the MMF-treated group (p = 0.04). MMF and tacrolimus could promote BKV viraemia after renal transplantation. Discontinuation of MMF together with a reduction of calcineurin inhibitors and glucocorticoids could be an option to reduce BKV replication after renal transplantation.

Roles of ATM and ATR-Mediated DNA Damage Responses during Lytic BK Polyomavirus Infection

BK polyomavirus (BKPyV) is an emerging pathogen whose reactivation causes severe disease in transplant patients. Unfortunately, there is no specific anti-BKPyV treatment available, and host cell components that affect the infection outcome are not well characterized. In this report, we examined the relationship between BKPyV productive infection and the activation of the cellular DNA damage response (DDR) in natural host cells. Our results showed that both the ataxia-telangiectasia mutated (ATM)- and ATM and Rad-3-related (ATR)-mediated DDR were activated during BKPyV infection, accompanied by the accumulation of polyploid cells. We assessed the involvement of ATM and ATR during infection using small interfering RNA (siRNA) knockdowns. ATM knockdown did not significantly affect viral gene expression, but reduced BKPyV DNA replication and infectious progeny production. ATR knockdown had a slightly more dramatic effect on viral T antigen (TAg) and its modified forms, DNA replication, and progeny production. ATM and ATR double knockdown had an additive effect on DNA replication and resulted in a severe reduction in viral titer. While ATM mainly led to the activation of pChk2 and ATR was primarily responsible for the activation of pChk1, knockdown of all three major phosphatidylinositol 3-kinase-like kinases (ATM, ATR, and DNA-PKcs) did not abolish the activation of γH2AX during BKPyV infection. Finally, in the absence of ATM or ATR, BKPyV infection caused severe DNA damage and aberrant TAg staining patterns. These results indicate that induction of the DDR by BKPyV is critical for productive infection, and that one of the functions of the DDR is to minimize the DNA damage which is generated during BKPyV infection.

Putative Episodes of T-Cell–Mediated Rejection in Patients With Sustained BK Viruria but No Viremia

Polyomavirus BK (BKV) infection characterized by viruria alone is considered to be of little clinical significance, but this issue has not been systematically studied. We studied 230 patients with sustained viruria from whom multiple samples taken after a median of 877 days (range, 24-2739) showed no progression to viremia or nephropathy. Biopsies satisfying Banff thresholds for inflammation and tubulitis in the presence of viruria but negative for BKV stains were designated as putative T-cell-mediated acute rejection. Compared with no viruria (n=515), sustained viruria was associated with more putative rejection episodes (0.62 vs. 0.33 per patient, P=0.006) and greater incidence of steroid resistance (36.2% vs. 19.6%, P=0.002). Most putative rejection episodes (52.1%) occurred concurrently with viruria, with a minority before (7.8%) or after (40.1%) BKV clearance. Steroid resistance was more frequent in putative rejection with concurrent viruria (48.6%), compared with rejection before (9.1%) or after (26.0%) viral clearance. These observations remained valid even on a separate analysis of patients with BKV load 1E+07 copies per mL or less. As assessed by the slope of reciprocal serum creatinine levels, accelerated deterioration of graft function resulted from rejection episodes occurring more than 2 years after transplantation. These observations indicate that intrarenal viral replication in sustained viruria is frequently associated with putative acute rejection. The implications of this association on the development of immune tolerance deserve further investigation.

Neutralization serotyping of BK polyomavirus infection in kidney transplant recipients.

BK polyomavirus (BKV or BKPyV) associated nephropathy affects up to 10% of kidney transplant recipients (KTRs). BKV isolates are categorized into four genotypes. It is currently unclear whether the four genotypes are also serotypes. To address this issue, we developed high-throughput serological assays based on antibody-mediated neutralization of BKV genotype I and IV reporter vectors (pseudoviruses). Neutralization-based testing of sera from mice immunized with BKV-I or BKV-IV virus-like particles (VLPs) or sera from naturally infected human subjects revealed that BKV-I specific serum antibodies are poorly neutralizing against BKV-IV and vice versa. The fact that BKV-I and BKV-IV are distinct serotypes was less evident in traditional VLP-based ELISAs. BKV-I and BKV-IV neutralization assays were used to examine BKV type-specific neutralizing antibody responses in KTRs at various time points after transplantation. At study entry, sera from 5% and 49% of KTRs showed no detectable neutralizing activity for BKV-I or BKV-IV neutralization, respectively. By one year after transplantation, all KTRs were neutralization seropositive for BKV-I, and 43% of the initially BKV-IV seronegative subjects showed evidence of acute seroconversion for BKV-IV neutralization. The results suggest a model in which BKV-IV-specific seroconversion reflects a de novo BKV-IV infection in KTRs who initially lack protective antibody responses capable of neutralizing genotype IV BKVs. If this model is correct, it suggests that pre-vaccinating prospective KTRs with a multivalent VLP-based vaccine against all BKV serotypes, or administration of BKV-neutralizing antibodies, might offer protection against graft loss or dysfunction due to BKV associated nephropathy.

Molecular Networks Involved in the Immune Control of BK Polyomavirus

BK polyomavirus infection is the important cause of virus-related nephropathy following kidney transplantation. BK virus reactivates in 30%–80% of kidney transplant recipients resulting in BK virus-related nephropathy in 1%–10% of cases. Currently, the molecular processes associated with asymptomatic infections in transplant patients infected with BK virus remain unclear. In this study we evaluate intrarenal molecular processes during different stages of BKV infection. The gene expression profiles of 90 target genes known to be associated with immune response were evaluated in kidney graft biopsy material using TaqMan low density array. Three patient groups were examined: control patients with no evidence of BK virus reactivation (n = 11), infected asymptomatic patients (n = 9), and patients with BK virus nephropathy (n = 10). Analysis of biopsies from asymptomatic viruria patients resulted in the identification of 5 differentially expressed genes (CD3E, CD68, CCR2, ICAM-1, and SKI) (P < 0.05), and functional analysis showed a significantly heightened presence of costimulatory signals (e.g., CD40/CD40L; P < 0.05). Gene ontology analysis revealed several biological networks associated with BKV immune control in comparison to the control group. This study demonstrated that asymptomatic BK viruria is associated with a different intrarenal regulation of several genes implicating in antiviral immune response.

Evaluation of virus-specific cellular immune response in transplant patients.

Virus-specific immune responses have a major impact on the outcome of the infection. Viral agents that are characterized by latency, such as herpesviruses and polyomaviruses, require a continuous immune control to reduce the extent of viral reactivation, as viral clearance cannot be accomplished, independently from the anti-viral treatment. In transplant patients, morbidity and mortality related to viral infections are significantly increased. In fact, the key steps of activation of T-cells are major target for anti-rejection immunosuppressive therapy and anti-viral immune response may be altered when infected cells and cellular effectors of immune response coexist in a transplanted organ. The role of cellular immune response in controlling viral replication and the main methods employed for its evaluation will be discussed. In particular, the main features, including both advantages and limitations, of available assays, including intracellular cytokine staining, major histocompatibility complex - multimer-based assays, Elispot assay, and QuantiFERON test, will be described. The potential applications of these assays in the transplant context will be discussed, particularly in relation to cytomegalovirus and polyomavirus BK infection. The relevance of introducing viro-immunological monitoring, beside virological monitoring, in order to identify the risk profile for viral infections in the transplant patients will allows for define a patient-tailored clinical management, particular in terms of modulation of immunosuppressive therapy and anti-viral administration.

The Status of BK Polyomavirus Replication in Adult Renal Transplant Recipients in Northeastern Poland

Purpose BK polyomavirus (BKV) infection and BKV-associated nephropathy (BKVAN) are among the most important problems in renal transplantation. We aimed to determine the incidence of BK viruria, viremia, and BKVAN in renal transplant recipients in the northeastern part of Poland. Methods Urine and blood samples from 126 cadaveric renal transplant recipients were analyzed for BK viruria and viremia using quantitative real-time polymerase chain reaction and the patients were followed prospectively. The diagnosis of BKVAN was established on the allograft biopsy. Results Based on the BKV DNA analysis, the patients were divided into three groups: group 1 ( n = 89; 70.6%) without viruria or viremia, group 2 ( n = 24; 19.1%) with isolated viruria, and group 3 ( n = 13; 10.3%) with both viruria and viremia. The presence of BK viremia negatively correlated with time after the transplantation. BK viruria was associated with mycophenolate mofetil daily dose. In group 3 there were four patients (3.2%) with high viremia (>10 4 genome equivalents [gEq]/mL) and viruria (>10 7 gEq/mL) loads. Only one patient from this group developed clinical symptoms and had BKVAN in allograft biopsy. In all four cases, the maintenance immunosuppression therapy was based on tacrolimus and steroids. Conclusion Prevalence of BKV infection in renal transplant recipients in the northeastern part of Poland is similar to that reported by studies from other countries. We confirm that BK viremia could be predicted by the presence of intense viruria. Time after transplantation and the type of immunosuppression strategy are the most important predictors of BK viremia and viruria in patients after renal transplantation.

UP-02.101 BK Polyomavirus Infection in Prostate Tissue Derived from Patients with Prostate Adenocarcinoma

BK polyomavirus (BKV) has been proposed to be involved in the etiology of prostate cancer. As persistent infection with BKV in prostate tissue may be a prerequisite for this hypothesis, we examined whether BKV DNA sequences are prevalent in tissues of prostate adenocarcinoma, and investigate the potential role of BKV in prostate tumorigenesis.