-
Viruses Jul 2022BK virus maintains a latent infection that is ubiquitous in humans. It has a propensity for reactivation in the setting of a dysfunctional cellular immune response and... (Review)
Review
BK virus maintains a latent infection that is ubiquitous in humans. It has a propensity for reactivation in the setting of a dysfunctional cellular immune response and is frequently encountered in kidney transplant recipients. Screening for the virus has been effective in preventing progression to nephropathy and graft loss. However, it can be a diagnostic and therapeutic challenge. In this in-depth state-of-the-art review, we will discuss the history of the virus, virology, epidemiology, cellular response, pathogenesis, methods of screening and diagnosis, evidence-based treatment strategies, and upcoming therapeutics, along with the issue of re-transplantation in patients.
Topics: BK Virus; Humans; Kidney Transplantation; Polyomavirus Infections; Tumor Virus Infections; Viremia
PubMed: 35893681
DOI: 10.3390/v14081616 -
Genes Jul 2022Poliomavirus BK virus (BKV) is highly infective, causing asymptomatic infections during childhood. After the initial infection, a stable state of latent infection is... (Review)
Review
Poliomavirus BK virus (BKV) is highly infective, causing asymptomatic infections during childhood. After the initial infection, a stable state of latent infection is recognized in kidney tubular cells and the uroepithelium with negligible clinical consequences. BKV is an important risk factor for BKV-associated diseases, and, in particular, for BKV-associated nephropathy (BKVN) in renal transplanted recipients (RTRs). BKVN affects up to 10% of renal transplanted recipients, and results in graft loss in up to 50% of those affected. Unfortunately, treatments for BK virus infection are restricted, and there is no efficient prophylaxis. In addition, consequent immunosuppressive therapy reduction contributes to immune rejection. Increasing surveillance and early diagnosis based upon easy and rapid analyses are resulting in more beneficial outcomes. In this report, the current status and perspectives in the diagnosis and treatment of BKV in RTRs are reviewed.
Topics: BK Virus; Humans; Immunosuppressive Agents; Kidney; Kidney Diseases; Kidney Transplantation; Polyomavirus Infections; Tumor Virus Infections
PubMed: 35886073
DOI: 10.3390/genes13071290 -
Experimental and Clinical... Nov 2020The BK polyomavirus was isolated in 1971; it has been a significant risk factor for both graft dysfunction and failure in renal transplant recipients. So far, no... (Review)
Review
The BK polyomavirus was isolated in 1971; it has been a significant risk factor for both graft dysfunction and failure in renal transplant recipients. So far, no specific treatment option has been available for effective treatment or prophylaxis for BK virus infections. Although the use of heavy immunosuppression has been the main risk factor for BK virus infection, other risk factors are equally important, including elderly recipients, prior rejection episodes, male sex, human leukocyte antigen mismatching, prolonged cold ischemia time, pretransplant BK virus serostatus, and ureteral stenting. Regular follow-up for BK virus infections according to each institution's policy has been, so far, effective in detecting patients with BK virus viremia and consequently preventing allograft loss. The mainstay of management continues to be reduction of immunosuppression. However, newer options are providing new insights, such as cellular immunotherapy. In this review, we will address the diagnosis, screening, new diagnostic tools, and updated management of BK virus infections.
Topics: Adoptive Transfer; Antiviral Agents; BK Virus; Drug Substitution; Humans; Immunocompromised Host; Immunoglobulins, Intravenous; Immunosuppressive Agents; Immunotherapy; Kidney Transplantation; Opportunistic Infections; Polyomavirus Infections; Risk Assessment; Risk Factors; Treatment Outcome; Tumor Virus Infections
PubMed: 32552624
DOI: 10.6002/ect.2019.0254 -
Viruses Jul 2020Human BK polyomavirus (BKPyV) prevalence has been increasing due to the introduction of more potent immunosuppressive agents in transplant recipients, and its clinical...
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 , 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 genotyping and a novel algorithm for NCCR block identification. genotyping is based on a modified implementation of the (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.
Topics: Algorithms; BK Virus; Capsid Proteins; Genetic Variation; Genotyping Techniques; Phylogeny; RNA, Untranslated; Software; Virus Replication
PubMed: 32751885
DOI: 10.3390/v12080837 -
American Journal of Transplantation :... Aug 2017
Topics: BK Virus; Humans; Kidney Diseases; Polyomavirus Infections
PubMed: 28510315
DOI: 10.1111/ajt.14358 -
Viruses Nov 2017The BK virus (BKPyV) is a member of the family first isolated in 1971. BKPyV causes frequent infections during childhood and establishes persistent infections with... (Review)
Review
The BK virus (BKPyV) is a member of the family first isolated in 1971. BKPyV causes frequent infections during childhood and establishes persistent infections with minimal clinical implications within renal tubular cells and the urothelium. However, reactivation of BKPyV in immunocompromised individuals may cause serious complications. In particular, with the implementation of more potent immunosuppressive drugs in the last decade, BKPyV has become an emerging pathogen in kidney and bone marrow transplant recipients where it often causes associated nephropathy and haemorrhagic cystitis, respectively. Unfortunately, no specific antiviral against BKPyV has been approved yet and the only therapeutic option is a modulation of the immunosuppressive drug regimen to improve immune control though it may increase the risk of rejection. A better understanding of the BKPyV life cycle is thus needed to develop efficient treatment against this virus. In this review, we provide an update on recent advances in understanding the biology of BKPyV.
Topics: Antiviral Agents; BK Virus; Humans; Immunocompromised Host; Immunosuppressive Agents; Polyomavirus Infections; Transplant Recipients; Virus Activation
PubMed: 29099746
DOI: 10.3390/v9110327 -
The New Microbiologica May 2023BK virus (BKV) associated with hemorrhagic cystitis (HC) is the most important complication that develops after hematopoietic stem cell transplantation (HSCT) in...
BK virus (BKV) associated with hemorrhagic cystitis (HC) is the most important complication that develops after hematopoietic stem cell transplantation (HSCT) in patients with hematological malignancies. This study aims to investigate BKV infections and HC in pediatric patients after allogeneic hematopoietic stem cell transplantation. Between November 2018 and November 2019, a total of 51 patients between the ages of 11 months and 17 years were included in the study. BKV Bosphore ® v1 quantification kit (Geneworks Anatolia, Turkey) was used for the detection of BKV DNA in urine and blood samples. Among the total of 51 patients, the incidence of BKV infection was found to be 86.3%. Allogeneic HSCT was performed in 40 patients and autologous HSCT in 11 patients. BK viruria and/or viremia were detected in 85% (44) of patients who underwent allogeneic HSCT and in 90% in the autologous group. High-level BK viruria (>107 copies/mL) was found in 41% (9) of 22 patients who were BKV positive before transplantation, while in 27.5% (8) of 29 patients who were BKV negative before transplantation; thus, BKV positivity before transplantation was considered a risk factor for high-level BK viruria. Acute GVHD developed in 6 of 40 patients in the allogeneic group. HC was prevented in 12 (67%) of 18 patients who received preemptive treatment, while HC developed in 6 (33%). HC occurred at a median of 35 days (17-49 days) post-transplant. Despite preemptive treatment, 6 (15%) patients who developed HC associated with BKV were in the allogeneic group but not in the autologous group. Of these patients with HC, 5 received a myeloablative treatment regimen, and 1 patient was given a reduced-intensity treatment regimen. The viral load in urine was found to be 107-9 copies/mL within 2 weeks before the development of HC and has been identified as a prognostic indicator. In conclusion, early diagnosis of viral infections by monitoring BKV viral load in HSCT patients will be effective in preventing the progression of complications such as BKV-associated HC by providing timely initiation of preemptive treatment.
Topics: Humans; Child; Infant; Cystitis; Risk Factors; Hematopoietic Stem Cell Transplantation; Polyomavirus Infections; Transplant Recipients; BK Virus; Hemorrhage
PubMed: 37247234
DOI: No ID Found -
Experimental and Clinical... Aug 2016BK virus nephropathy is a challenging clinical problem in kidney transplant recipients with wide range of surveillance and management practices, based on individual... (Review)
Review
BK virus nephropathy is a challenging clinical problem in kidney transplant recipients with wide range of surveillance and management practices, based on individual experience. BK virus reactivation in kidney transplant recipients can result in BK virus nephropathy and graft loss. The most effective strategy for early diagnosis and treatment of BK virus nephropathy is regular monitoring for BK virus, currently achieved by quantification of viral DNA in blood by quantitative polymerase chain reaction. Immunosuppression reduction remains the mainstay of treatment; however, viral clearance is often followed by acute rejection, likely secondary to a delay between immune reconstitution and viral clearance. Impaired cell-mediated immune response to BK virus has been shown to correlate with progression to BK virus nephropathy, while reconstitution of this response correlates with resolution of nephropathy. There is recent research to support monitoring BK virus-specific cell-mediated immune response as a predictor of disease progression and resolution. In this article, we review the current concepts and recent developments in understanding BK virus-associated disease in the context of kidney transplant and outline areas for future research.
Topics: Antiviral Agents; BK Virus; Drug Therapy, Combination; Graft Rejection; Graft Survival; Host-Pathogen Interactions; Humans; Immunocompromised Host; Immunosuppressive Agents; Kidney Transplantation; Opportunistic Infections; Polyomavirus Infections; Risk Factors; Treatment Outcome; Tumor Virus Infections; Virus Activation
PubMed: 27267780
DOI: 10.6002/ect.2016.0030 -
Pre-Transplantation Assessment of BK Virus Serostatus: Significance, Current Methods, and Obstacles.Viruses Oct 2019The immunosuppression required for graft tolerance in kidney transplant patients can trigger latent BK polyomavirus (BKPyV) reactivation, and the infection can progress... (Review)
Review
The immunosuppression required for graft tolerance in kidney transplant patients can trigger latent BK polyomavirus (BKPyV) reactivation, and the infection can progress to nephropathy and graft rejection. It has been suggested that pre-transplantation BKPyV serostatus in donors and recipients is a predictive marker for post-transplantation BKPyV replication. The fact that research laboratories have used many different assay techniques to determine BKPyV serostatus complicates these data analysis. Even studies based on the same technique differed in their standard controls choice, the antigenic structure type used for detection, and the cut-off for seropositivity. Here, we review the different BKPyV VP1 antigens types used for detection and consider the various BKPyV serostatus assay techniques' advantages and disadvantages. Lastly, we highlight the obstacles in the implementation of a consensual BKPyV serologic assay in clinics (e.g., the guidelines absence in this field).
Topics: BK Virus; DNA, Viral; Graft Rejection; Humans; Immunosuppression Therapy; Kidney Transplantation; Retrospective Studies; Serologic Tests; Transplant Recipients; Tumor Virus Infections; Viremia
PubMed: 31615131
DOI: 10.3390/v11100945 -
Reviews in Medical Virology Jul 2020BK polyomavirus (BKPyV or BKV) is a non-enveloped, circular double-stranded DNA virus that may exceed 80% seroprevalence in adults. BKV infection typically occurs during... (Review)
Review
BK polyomavirus (BKPyV or BKV) is a non-enveloped, circular double-stranded DNA virus that may exceed 80% seroprevalence in adults. BKV infection typically occurs during childhood, and the majority of adults are latently infected. While BKV infection is rarely associated with clinical disease in most individuals, in immunosuppressed individuals, reactivation may cause kidney (BK-associated nephropathy) or bladder (hemorrhagic cystitis and ureteral stenosis) injury. No antiviral therapies have been approved for the treatment of BKV infection. Reducing immunosuppression is the most effective therapy, although this is not feasible in many patients. Thus, a robust understanding of viral pathogenesis and viral diversity remains important for the development of future therapeutic strategies. Studies of BKV diversity are quite sparse compared to other common viral infections; thus, much of our understanding of BVK variability and evolution relies heavily analogous studies of other viruses such as HIV or viral hepatitis. We provide a comprehensive review of BKV diversity at the population and individual level with careful consideration of how viral variability may impact viral replication, pathogenesis, tropism, and protein function. We also discuss a number of outstanding questions related to BK virus diversity that should be explored rigorously in future studies.
Topics: Animals; BK Virus; Biodiversity; Evolution, Molecular; Genetic Variation; Genome, Viral; Genomics; Humans; Phylogeny; Polyomavirus Infections
PubMed: 32128960
DOI: 10.1002/rmv.2102