scholarly journals BKTyper: Free Online Tool for Polyoma BK Virus VP1 and NCCR Typing

Viruses ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 837
Author(s):  
Joan Martí-Carreras ◽  
Olga Mineeva-Sangwo ◽  
Dimitrios Topalis ◽  
Robert Snoeck ◽  
Graciela Andrei ◽  
...  

Human BK polyomavirus (BKPyV) prevalence has been increasing due to the introduction of more potent immunosuppressive agents in transplant recipients, and its clinical interest. BKPyV has been linked mostly to polyomavirus-associated hemorrhagic cystitis, in allogenic hematopoietic stem cell transplant, and polyomavirus-associated nephropathy in kidney transplant patients. BKPyV is a circular double-stranded DNA virus that encodes for seven proteins, of which Viral Protein 1 (VP1), the major structural protein, has been extensively used for genotyping. BKPyV also contains the noncoding control region (NCCR), configured by five repeat blocks (OPQRS) known to be highly repetitive and diverse, and linked to viral infectivity and replication. BKPyV genetic diversity has been mainly studied based on the NCCR and VP1, due to the high occurrence of BKPyV-associated diseases in transplant patients and their clinical implications. Here BKTyper is presented, a free online genotyper for BKPyV, based on a VP1 genotyping and a novel algorithm for NCCR block identification. VP1 genotyping is based on a modified implementation of the BK typing and grouping regions (BKTGR) algorithm, providing a maximum-likelihood phylogenetic tree using a custom internal BKPyV database. Novel NCCR block identification relies on a minimum of 12-bp motif recognition and a novel sorting algorithm. A graphical representation of the OPQRS block organization is provided.

2017 ◽  
Vol 9 (2) ◽  
Author(s):  
Duygu Mert ◽  
Hikmetullah Batgi ◽  
Alparslan Merdin ◽  
Sabahat Çeken ◽  
Mehmet Sinan Dal ◽  
...  

BK virus is a human polyoma virus. It is acquired in early childhood and remains life-long latent in the genitourinary system. BK virus replication is more common in receiving immunosuppressive therapy receiving patients and transplant patients. BK virus could cause hemorrhagic cystitis in patients with allogeneic stem cell transplantation. Hemorrhagic cystitis is a serious complication of hematopoietic stem cell transplantation. Hemorrhagic cystitis could cause morbidity and long stay in the hospital. Diagnosis is more frequently determined by the presence of BK virus DNA detected with quantitative or real-time PCR testing in serum or plasma and less often in urine. The reduction of immunosuppression is effective in the treatment of BK virus infection. There are also several agents with anti-BK virus activity. Cidofovir is an active agent against a variety of DNA viruses including poliomyoma viruses and it is a cytosine nucleotide analogue. Intravenous immunoglobulin IgG (IVIG) also includes antibodies against BK and JC (John Cunningham) viruses. Hereby, we report three cases of hemorrhagic cystitis. Hemorrhagic cystitis developed in all these three cases of allogeneic stem cell transplantation due to acute myeloid leukemia (AML). BK virus were detected as the cause of hemorrhagic cystitis in these patients. Irrigation of the bladder was performed. Then levofloxacin 1×750 mg intravenous and IVIG 0.5 gr/kg were started. But the hematuria did not decreased. In the first case, treatment with leflunomide was started, but patient died due to refractory AML and severe graft-versus-host disease after 4th day of leflunamide and levofloxacin treatments. Cidofovir treatment and the reduction of immunosuppressive treatment decreased the BK virus load and resulted symptomatic improvement in the second case. Initiation of cidofovir was planned in the third case. Administration of cidofovir together with the reduction of immunosuppression in the treatment of hemorrhagic cystitis associated with BK virus in allogeneic stem cell transplant recipients could be a good option.


2017 ◽  
Vol 2017 ◽  
pp. 1-5 ◽  
Author(s):  
Luciana Antoniolli ◽  
Rafael Borges ◽  
Luciano Z. Goldani

Encephalitis and meningitis due to BKPyV are unusual and emerging condition. Only a few cases of BKPyV encephalitis have been reported in hematopoietic stem cell transplant recipients, with the majority of cases presenting with concurrent hemorrhagic cystitis and HIV-infected patients. The authors report two HIV-infected patients with the diagnosis of BKPyV encephalitis and discuss the main clinical, diagnostic, and therapeutic aspects of this infection in patients with AIDS. Physicians should be aware to recognize the main clinical features and diagnose BKPyV central nervous infection in the setting of AIDS.


Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4468-4468
Author(s):  
Devi D Morrison ◽  
Samith Thomas Kochuparambil ◽  
David Deremer ◽  
Ethan Speir ◽  
Kristen Sterling ◽  
...  

Abstract Abstract 4468 Introduction: BK viuria is an important and frequent infection in the post-allogeneic hematopoietic stem cell transplant (allo-HSCT) setting that results in significant morbidity and mortality. Over the years our understanding of the disease process has improved significantly but treatment algorithms remain poorly defined and developed. A variety of anti-viral therapies have been utilized in conjunction with reduced immunosuppression with modest benefits. We therefore present our institutional data and recommend a clinical practice guideline that could potentially improve the outcomes of patients with BK-virus infections. Method: Our retrospective analysis included 75 consecutive patients who underwent allo-HSCT from 2001–2011. Data was collected on patients with PCR proven BK-viuria under existing IRB approved protocols. SPSS version 13.0 was used for statistical analysis. Kaplan-Meier method was used to calculate survival outcomes. Result: 12% (9/75) of all patients developed PCR proven hemorrhagic cystitis (HC). The median age of patients at transplant was 37-years (range 28–61). 77% were male. 66% had acute myeloid or lymphoblastic leukemia and the median number of prior therapies was three. 33% had a matched unrelated donor transplant while 66% received reduced intensity conditioning regimen and 33% received anti-thymocyte globulin (ATG). The mean CD34+ cell dose infused was 4.8×106/kg and the mean CD3+ cell dose was 8.6×1011/kg. Median days to neutrophil engraftment were 11 and for platelet engraftment were 14. The median ECOG performance status was 1 (range 0–2). The median time of onset of HC from day 0 of transplant was 44-days (range 4–158) and lasted for an average of 53-days (range 7–157). 33% patients were neutropenic at the onset of HC and the mean absolute neutrophil count was 4300/ul. Most common symptoms were dysuria in 66%, bladder spasms in 44% and urinary retention in 22%. All patients had received GVHD prophylaxis with methotrexate and tacrolimus and 77% were on concurrent steroids and mycophenolate. 88% of patients had concurrent acute graft-vs.-host disease (GVHD) at the time of HC. 88% also had concurrent CMV viremia and 11% had EBV viremia at the time of HC. 44% developed BK-viremia while 55% had BK-virus induced nephropathy defined as an increase of serum creatinine >1.5. Management approach was tiered into prophylaxis, symptomatic relief and anti-viral therapy. All patients received ciprofloxacin and 88% received intravenous immunoglobulin (IVIg). No single therapy component including reduced immunosuppression, cidofovir and leflunomide was independently identified as a more efficacious option (p>0.05) but of the patients who received cidofovir, 75% had resolution of symptoms and were able to clear the BK-viuria with the median duration of treatment of 4.5 weeks. Conclusion: Our analysis supports existing data that BK-virus induced HC is the result of multifaceted host and donor interactions and the concurrent use of immune altering therapies. To address the need of reduced morbidity and improved outcomes of this commonly encountered scenario in the post allo-HSCT setting, we have developed a multi-tiered approach that includes prophylactic intervention with ciprofloxacin for patients undergoing T-cell depleting regimens; symptomatic management with continuous bladder irrigation, pyridium and oxybutynin; and antiviral therapy with cidofovir and leflunomide in select subsets of patients. This approach will provide us a tool to uniformly manage our patients with BK-viuria and HC, and continually analyze and improve outcomes in a prospective manner. Disclosures: No relevant conflicts of interest to declare.


2019 ◽  
Vol 54 (6) ◽  
pp. 547-553 ◽  
Author(s):  
Graham M. Tooker ◽  
Kristen A. Stafford ◽  
Jennifer Nishioka ◽  
Ashraf Z. Badros ◽  
David J. Riedel

Background: BK virus hemorrhagic cystitis (BKV-HC) is a common complication following hematopoietic stem cell transplant (HSCT); optimal management remains uncertain. Supportive care (bladder irrigation and blood transfusions) and intravenous and intravesicular cidofovir have all been used with varying success. Objective: The purpose of this study was to determine the safety and effectiveness of intravesicular cidofovir for BKV-HC following HSCT. Methods: A retrospective analysis of all HSCT patients with BKV-HC prescribed intravesicular cidofovir from 2012 to 2017. Results: 33 patients were treated for BKV-HC. The median age was 50 years (range 23-73), and 18 (55%) were male. The median HC symptom severity was 2, with a median BK urine viral load pretreatment of 100,000,000 IU/mL. Patients received a median of 2 intravesicular treatments (range 1-7) at a dosage of 5 mg/kg per instillation. In all, 19 (59%) patients demonstrated complete clinical resolution of symptoms; 9 (28%) had a partial response; and 4 (13%) had no change in symptoms. Patients with a high pretreatment BK viral load (>100 million) and high HC grade (2-4) had a lower frequency of complete remission. The main side effect of intravesicular instillation was severe bladder spasms in 4 patients (12%). Conclusion and Relevance: This is the largest study of intravesicular cidofovir treatment of BKV HC reported to date; 88% of patients with BVK-HC achieved clinical improvement of symptoms with minimal side effects. Clinical trials of intravesicular cidofovir could provide further evidence for this treatment for BKV-HC.


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