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Biology of Blood and Marrow... Mar 2018Virus infection remains an appreciable cause of morbidity and mortality after hematopoietic stem cell transplantation (HSCT). Although pharmacotherapy and/or antibody... (Review)
Review
Virus infection remains an appreciable cause of morbidity and mortality after hematopoietic stem cell transplantation (HSCT). Although pharmacotherapy and/or antibody therapy may help prevent or treat viral disease, these drugs are expensive, toxic, and often ineffective due to primary or secondary resistance. Further, effective treatments are limited for many infections (eg, adenovirus, BK virus), which are increasingly detected after alternative donor transplants. These deficiencies in conventional therapeutics have increased interest in an immunotherapeutic approach to viral disorders, leading to adoptive transfer of virus-specific cytotoxic T lymphocytes (VSTs), which can rapidly reconstitute antiviral immunity post-transplantation without causing graft-versus-host disease. This review will explore how the VST field has improved outcomes for many patients with life-threatening viral infections after HSCT, and how to broaden applicability beyond the "patient-specific" products, as well as extending to other viral diseases even outside the context of HSCT.
PubMed: 29425515
DOI: 10.1016/j.bbmt.2017.12.787 -
Frontiers in Cellular and Infection... 2023The identification of the first human polyomavirus BK (BKV) has been over half century, The previous epidemiological and phylogenetic studies suggest that BKV prevailed... (Review)
Review
The identification of the first human polyomavirus BK (BKV) has been over half century, The previous epidemiological and phylogenetic studies suggest that BKV prevailed and co-evolved with humans, leading to high seroprevalence all over the world. In general, BKV stays latent and symptomless reactivation in healthy individuals. BKV has been mainly interlinked with BKV-associated nephropathy (BKVAN) in kidney-transplant recipients and hemorrhagic cystitis (HC) in hematopoietic stem cell transplant recipients (HSCTRs). However, the mechanisms underlying BKV latency and reactivation are not fully understood and lack of extensive debate. As Merkel cell polyomavirus (MCV) was identified as a pathogenic agent of malignant cutaneous cancer Merkel cell carcinoma (MCC) since 2008, linking BKV to tumorigenesis of urologic tumors raised concerns in the scientific community. In this review, we mainly focus on advances of mechanisms of BKV latency and reactivation, and BKV-associated diseases or tumorigenesis with systematical review of formerly published papers following the PRISMA guidelines. The potential tumorigenesis of BKV in two major types of cancers, head and neck cancer and urologic cancer, was systematically updated and discussed in depth. Besides, BKV may also play an infectious role contributing to HIV-associated salivary gland disease (HIVSGD) presentation. As more evidence indicates the key role of BKV in potential tumorigenesis, it is important to pay more attention on its etiology and pathogenicity and .
Topics: Humans; BK Virus; Phylogeny; Seroepidemiologic Studies; Polyomavirus Infections; Carcinogenesis; Cell Transformation, Neoplastic
PubMed: 37771695
DOI: 10.3389/fcimb.2023.1263983 -
Scientific Reports Jan 2021BK virus associated nephropathy (BKN) is an important cause of kidney allograft failure. In a cohort of paediatric kidney transplant recipients, we aimed to understand...
BK virus associated nephropathy (BKN) is an important cause of kidney allograft failure. In a cohort of paediatric kidney transplant recipients, we aimed to understand the incidence and clinical outcome associated with BKN, as well as identify risk factors for BKN and BK viraemia development. We retrospectively analysed all patients who received a kidney transplant and received follow up care in our centre between 2009-2019. Among 106 patients included in the study (mean follow up 4.5 years), 32/106 (30.2%) patients experienced BK viraemia. The incidence of BKN was 7/106 (6.6%). The median time of BK viraemia development post-transplant was 279.5 days compared to 90.0 days for BKN. Development of BKN was associated with younger age at transplantation (p = 0.013). Development of BK viraemia was associated with negative recipient serology for cytomegalovirus (CMV) at time of transplantation (p = 0.012) and a higher net level of immunosuppression (p = 0.039). There was no difference in graft function at latest follow up between those who experienced BKN and those without BKN. This study demonstrates that BK virus infection is associated with younger age at transplantation, CMV negative recipient serostatus and higher levels of immunosuppression. Judicious monitoring of BK viraemia in paediatric transplant recipients, coupled with timely clinical intervention can result in similar long-term outcomes for BKN patients compared to controls.
Topics: Aftercare; Age Factors; BK Virus; Child; Female; Graft Rejection; Humans; Incidence; Kidney Diseases; Kidney Transplantation; Male; Polyomavirus Infections; Retrospective Studies; Viremia
PubMed: 33510329
DOI: 10.1038/s41598-021-82160-0 -
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 -
Central European Journal of Urology 2020The polyomaviruses are omnipresent in nature. The major sites of BK virus appearance are the kidney tubular epithelial cells and urinary bladder surface transitional... (Review)
Review
INTRODUCTION
The polyomaviruses are omnipresent in nature. The major sites of BK virus appearance are the kidney tubular epithelial cells and urinary bladder surface transitional cells.
MATERIAL AND METHODS
A literature search according to PRISMA guidelines within the Medline database was conducted in July 2019 for articles presenting data about BK virus in urologic aspect without setting time limits, using the terms 'BK virus' in conjunction with transplantation, nephropathy, stenosis, cancer, bladder, prostate, kidney.
RESULTS
The BK virus usually stays latent, however, its replication may become active in various clinical situations of impaired immunocompetence such as solid organ transplantation, bone marrow transplantation, AIDS, pregnancy, multiple sclerosis, administration of chemotherapy or biologic therapy. BK virus is associated with two main complications after transplantation: polyomavirus-associated nephropathy in kidney transplant patients and polyomavirus-associated hemorrhagic cystitis in allogeneic hematopoietic stem cell transplant patients.
CONCLUSIONS
The aim of this article was to present available data on urologic aspects of BK virus infection, its detection methods and available treatment.
PubMed: 32395331
DOI: 10.5173/ceju.2020.0034 -
International Journal of Molecular... Dec 2023Polyomaviruses are widespread, with BK viruses being most common in humans who require immunosuppression due to allotransplantation. Infection with BK polyomavirus (BKV)...
Polyomaviruses are widespread, with BK viruses being most common in humans who require immunosuppression due to allotransplantation. Infection with BK polyomavirus (BKV) may manifest as BK virus-associated nephropathy and hemorrhagic cystitis. Established diagnostic methods include the detection of polyomavirus in urine and blood by PCR and in tissue biopsies via immunohistochemistry. In this study, 79 patients with pathological renal retention parameters and acute kidney injury (AKI) were screened for BK polyomavirus replication by RNA extraction, reverse transcription, and virus-specific qPCR in urine sediment cells. A short fragment of the VP2 coding region was the target of qPCR amplification; patients with (n = 31) and without (n = 48) a history of renal transplantation were included. Urine sediment cell immunofluorescence staining for VP1 BK polyomavirus protein was performed using confocal microscopy. In 22 patients with acute renal injury, urinary sediment cells from 11 participants with kidney transplantation (KTX) and from 11 non-kidney transplanted patients (nonKTX) were positive for BK virus replication. BK virus copies were found more frequently in patients with AKI stage III (n = 14). Higher copy numbers were detected in KTX patients having experienced BK polyoma-nephropathy (BKPyVAN) in the past or diagnosed recently by histology (5.6 × 10-3.1 × 10). One patient developed BK viremia following delayed graft function (DGF) with BK virus-positive urine sediment. In nonKTX patients with BK copies, decoy cells were absent; however, positive staining of cells was found with epithelial morphology. Decoy cells were only found in KTX patients with BKPyVAN. In AKI, damage to the tubular epithelium itself may render the epithelial cells more permissive for polyoma replication. This non-invasive diagnostic approach to assess BK polyomavirus replication in urine sediment cells has the potential to identify KTX patients at risk for viremia and BKPyVAN during AKI. This method might serve as a valuable screening tool for close monitoring and tailored immunosuppression decisions.
Topics: Humans; BK Virus; Viremia; Kidney Transplantation; Kidney; Polyomavirus; Polyomavirus Infections; Acute Kidney Injury
PubMed: 38139342
DOI: 10.3390/ijms242417511 -
Kidney Medicine 2020Reactivation of BK virus (BKV) remains a dreaded complication in immunosuppressed states. Conventionally, BKV is known as a cause for BKV-associated nephropathy and... (Review)
Review
Reactivation of BK virus (BKV) remains a dreaded complication in immunosuppressed states. Conventionally, BKV is known as a cause for BKV-associated nephropathy and allograft dysfunction in kidney transplant recipients. However, emerging studies have shown its negative impact on native kidney function and patient survival in other transplants and its potential role in diseases such as cancer. Because BKV-associated nephropathy is driven by immunosuppression, reduction in the latter is a convenient standard of care. However, this strategy is risk prone due to the development of donor-specific antibodies affecting long-term allograft survival. Despite its pathogenic role, there is a distinct lack of effective anti-BKV therapeutics. This limitation combined with increased morbidity and health care cost of BKV-associated diseases add to the complexity of BKV management. While summarizing recent advances in the pathogenesis of BKV-associated nephropathy and its reactivation in other organ transplants, this review illustrates the limitations of current and emerging therapeutic options and provides a compelling argument for an effective targeted anti-BKV drug.
PubMed: 33319201
DOI: 10.1016/j.xkme.2020.06.015 -
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 -
American Journal of Transplantation :... Feb 2016BK polyomavirus (BKPyV) infection represents a major problem in transplantation, particularly for renal recipients developing polyomavirus-associated nephropathy... (Review)
Review
BK polyomavirus (BKPyV) infection represents a major problem in transplantation, particularly for renal recipients developing polyomavirus-associated nephropathy (PyVAN). The possibility that BKPyV may also be oncogenic is not routinely considered. Twenty high-grade renourinary tumors expressing polyomavirus large T antigen in the entirety of the neoplasm in 19 cases, including the metastases in six, have been reported in transplant recipients with a history of PyVAN or evidence of BKPyV infection. Morphological and phenotypical features consistent with inactivation of the tumor suppressors pRB and p53 were found in the bladder tumors, suggesting a carcinogenesis mechanism involving the BKPyV large tumor oncoprotein/antigen. The pathogenesis of these tumors is unclear, but given the generally long interval between transplantation and tumor development, the risk for neoplasms after BKPyV infections may well be multifactorial. Other elements potentially implicated include exposure to additional exogenous carcinogens, further viral mutations, and cell genomic instability secondary to viral integration, as occurs with the Merkel cell PyV-associated carcinoma. The still scarce but increasingly reported association between longstanding PyVAN and renourinary neoplasms requires a concerted effort from the transplant community to better understand, diagnose, and treat the putative association between the BKPyV and these neoplasms.
Topics: BK Virus; Carcinogenesis; Humans; Kidney Diseases; Polyomavirus Infections; Prognosis; Tumor Virus Infections; Urinary Bladder Neoplasms
PubMed: 26731714
DOI: 10.1111/ajt.13550 -
Current Opinion in Organ Transplantation Jun 2015Polyomavirus nephropathy (PVN) mainly caused by BK virus (BKV) remains the most common productive viral infection of the kidney. Over the past decade, clinical interest... (Review)
Review
PURPOSE OF REVIEW
Polyomavirus nephropathy (PVN) mainly caused by BK virus (BKV) remains the most common productive viral infection of the kidney. Over the past decade, clinical interest often focused on BK viremia and viruria as the diagnostic mainstays of patient management. The purpose of this review is to discuss viral nephropathy in the context of BK viremia and viruria and new strategies to optimize diagnostic accuracy and patient management. The emerging roles of polyomaviruses in oncogenesis, salivary gland disease, and post-bone marrow transplantation as well as novel Polyomavirus strains are highlighted.
RECENT FINDINGS
Areas of investigation include proposals by the Banff working group on the classification of PVN and studies on PVN progression and resolution, including the role cellular immune responses may play during reconstitution injury. New noninvasive strategies to optimize the diagnosis of PVN, that is, the urinary 'polyomavirus-haufen' test and mRNA expression levels for BKV in the urine, hold great promise to accurately identify patients with viral nephropathy. Tools are now available to separate 'presumptive' from 'definitive' disease in various patient cohorts including individuals post-bone marrow transplantation. Recent observations also point to a currently underrecognized role of polyomaviruses in oncogenesis post-transplantation and salivary gland disease in patients with HIV-AIDS.
SUMMARY
This review summarizes recent studies on PVN and the significance of the BKV strain in disease. Current paradigms for patient management post-(renal) transplantation are discussed in the setting of new observations. Issues that still require clarification and further validation are highlighted.
Topics: Animals; BK Virus; Humans; Kidney Diseases; Kidney Transplantation; Polyomavirus Infections; Viremia
PubMed: 25933251
DOI: 10.1097/MOT.0000000000000192