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Viral Immunology Mar 2016Recent information demonstrated that BK virus reactivation is a dominant complication after kidney transplantation, which occurs because of immunosuppression. BK virus... (Review)
Review
Recent information demonstrated that BK virus reactivation is a dominant complication after kidney transplantation, which occurs because of immunosuppression. BK virus reactivation is the main reason of transplanted kidney losing. Immune response against BK virus is the major inhibitor of the virus reactivation. Therefore, improving our knowledge regarding the main parameters that fight against BK viruses can shed light on to direct new treatment strategies to suppress BK infection. Innate immunity consists of numerous cell systems and also soluble molecules, which not only suppress virus replication, but also activate adaptive immunity to eradicate the infection. Additionally, it appears that immune responses against reactivated BK virus are the main reasons for induction of BK virus-associated nephropathy (BKAN). Thus, improving our knowledge regarding the parameters and detailed mechanisms of innate immunity and also the status of innate immunity of the patients with BK virus reactivation and its complications can introduce new prospective strategies to either prevent or as therapy of the complication. Therefore, this review was aimed to collate the most recent data regarding the roles played by innate immunity against BK virus and also the status of innate immunity in the patients with reactivation BK virus and BKAN.
Topics: BK Virus; Host-Pathogen Interactions; Humans; Immunity, Innate; Polyomavirus Infections; Virus Activation; Virus Latency
PubMed: 26752693
DOI: 10.1089/vim.2015.0099 -
The Journal of Histochemistry and... May 2020BK polyomavirus-associated nephropathy (BKpyVAN) remains a cause of graft loss in kidney transplant recipients on immunosuppressive therapy. Its diagnosis relies on the...
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 ( = 0.65, 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.
Topics: BK Virus; Biopsy; Cohort Studies; DNA, Viral; Female; Humans; Kidney; Kidney Transplantation; Male; Middle Aged; Transplantation, Homologous
PubMed: 32352851
DOI: 10.1369/0022155420922604 -
Clinical Infectious Diseases : An... Jul 2001We present a review of the clinically oriented literature about BK virus, a relative of JC virus, which is the etiologic agent of progressive multifocal... (Review)
Review
We present a review of the clinically oriented literature about BK virus, a relative of JC virus, which is the etiologic agent of progressive multifocal leukoencephalopathy (PML). The kidney, lung, eye, liver, and brain have been proposed as sites of BK virus-associated disease, both primary and reactivated. BK virus has also been detected in tissue specimens from a variety of neoplasms. We believe that BK virus is most often permissively present in sites of disease in immunosuppressed patients, rather than being an etiologic agent that causes symptoms or pathologic findings. There is, however, strong evidence for BK virus-associated hemorrhagic cystitis and nephritis, especially in recipients of solid organ or bone marrow transplants. Now that BK virus can be identified by use of specific and sensitive techniques, careful evaluation of the clinical and pathologic presentations of patients with BK virus will allow us to form a clearer picture of viral-associated pathophysiology in many organ systems.
Topics: Animals; Autoimmune Diseases; BK Virus; Eye Diseases; Humans; Kidney Diseases; Liver Diseases; Lung Diseases; Neoplasms; Nervous System Diseases; Papillomavirus Infections; Tumor Virus Infections; Virus Latency
PubMed: 11418879
DOI: 10.1086/321813 -
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 -
Advances in Experimental Medicine and... 2006The last decade has witnessed the introduction of several potent immunosuppressive agents in the field of transplant medicine. Contemporaneously, infection with BK virus... (Review)
Review
The last decade has witnessed the introduction of several potent immunosuppressive agents in the field of transplant medicine. Contemporaneously, infection with BK virus (BKV) has emerged as an important complication of immunosuppression and an important cause of allograft loss after kidney transplantation. Rhandhawa et al reported the first case of BKV associated nephropathy (BKVN) in the modern era of transplantation, in 1995. Since then there has been a resurgence of interest in the epidemiology, biology and pathogenic associations of BKV especially in transplant medicine. Up to 90% of adults have serologic evidence of exposure to BKV. However, only 1-5% of normal healthy adults excrete the virus in the urine (asymptomatic viruria). Thus, for a vast majority of the population, the virus remains perfectly latent and this state of latency is of no obvious consequence. Almost all instances of disease by the BKV have been seen in immunocompromised patients. In recent years, BKV has been associated with nephropathy (BKVN) in about 5% of renal transplant patients. Once established, the disease may result in allograft loss in 45-70% of patients. Although not proven by any prospective study, BKVN causing allograft failure has been linked to immunosuppressive regimens containing tacrolimus or mycophenolate mofetil. This is noteworthy, as both these agents have been used increasingly as the primary maintenance immunotherapy in solid organ transplantation since their introduction around 1990. In addition to the immunosuppressed state, other factors like allograft injury have been thought to be involved in the pathogenesis of the disease. We believe that reactivation of the BKV from its latent state crucially depends on an immunocompromised state but more factors than one dictate precipitation of clinical end organ disease. In this Chapter, we will discuss the clinical aspects of BKV infection in the renal transplant recipient. We will focus on the role of immunosuppression as a seminal factor allowing replication of the virus. Not all patients who have replicating BKV go on to develop nephropathy: we will discuss other host factors that may constitute a 'second hit' allowing replicating BKV to precipitate BKVN. Results of our recently concluded prospective study on the issue of current immunosuppressive agents in the development of BKVN will be discussed. Finally, based on our experience, we will provide some guidelines for early diagnosis and management of this disease.
Topics: BK Virus; Humans; Immunosuppressive Agents; Kidney Transplantation; Polyomavirus Infections
PubMed: 16626035
DOI: 10.1007/0-387-32957-9_12 -
Clinical Journal of the American... Jul 2007Nephropathy from BK virus (BKV) infection is an evolving challenge in kidney transplant recipients. It is the consequence of modern potent immunosuppression aimed at... (Review)
Review
Nephropathy from BK virus (BKV) infection is an evolving challenge in kidney transplant recipients. It is the consequence of modern potent immunosuppression aimed at reducing acute rejection and improving allograft survival. Untreated BKV infections lead to kidney allograft dysfunction or loss. Decreased immunosuppression is the principle treatment but predisposes to acute and chronic rejection. Screening protocols for early detection and prevention of symptomatic BKV nephropathy have improved outcomes. Although no approved antiviral drug is available, leflunomide, cidofovir, quinolones, and intravenous Ig have been used. Retransplantation after BKV nephropathy has been successful.
Topics: Antiviral Agents; BK Virus; Graft Rejection; Humans; Immunosuppressive Agents; Kidney; Kidney Diseases; Kidney Transplantation; Mass Screening; Polyomavirus Infections; Reoperation; Severity of Illness Index; Time Factors
PubMed: 17699509
DOI: 10.2215/CJN.00920207 -
Advances in Experimental Medicine and... 2006Infection with BK virus (BKV), a member of the Polyomavirus (PV) family, is ubiquitous, with the virus remaining in a latent form in the kidney and urinary tract. This... (Review)
Review
Infection with BK virus (BKV), a member of the Polyomavirus (PV) family, is ubiquitous, with the virus remaining in a latent form in the kidney and urinary tract. This infection is usually asymptomatic, but with impairment of the cellular immune system the virus can reactivate and lead to tissue damage. In recipients of bone marrow and solid organ transplants, PV reactivation can be associated with disease in urinary tract and kidneys. BKV was first discovered in 1971 from the urine of a kidney transplant recipient who had developed ureteral stenosis 4 months after transplantation. While much of the subsequent research focuses on patients after renal transplantation, we will review PV impact in patients after bone marrow transplant (BMT) and those with non-renal solid organ transplants.
Topics: BK Virus; Humans; Polyomavirus Infections; Postoperative Complications; Transplantation, Homologous; Tumor Virus Infections
PubMed: 16626036
DOI: 10.1007/0-387-32957-9_13 -
Clinical Infectious Diseases : An... Aug 2005More than 70% of the general population worldwide has serological evidence of exposure to Polyomavirus hominis type 1, better known as BK virus (BKV). BKV infection... (Review)
Review
More than 70% of the general population worldwide has serological evidence of exposure to Polyomavirus hominis type 1, better known as BK virus (BKV). BKV infection typically occurs during childhood, without specific symptoms, followed by a state of nonreplicative infection in various tissues, with the urogenital tract as the principal site. Asymptomatic reactivation and low-level replication with viruria is observed in 5% of healthy individuals. Persistent high-level BKV replication is the hallmark of polyomavirus-associated nephropathy in renal transplantation and of hemorrhagic cystitis in bone marrow transplantation. Since these manifestations are rare in other types of immunocompromised patients, the presence of specific cofactors is postulated. The role of BKV in autoimmune disease and cancer is a controversial topic and is difficult to determine, because the pathology no longer depends on BKV replication. This article discusses current views of pathogenesis, diagnosis, and treatment.
Topics: BK Virus; Humans; Opportunistic Infections; Polyomavirus Infections; Tumor Virus Infections
PubMed: 16007533
DOI: 10.1086/431488 -
World Journal of Gastroenterology Jan 2016Polyomavirus BK (BKV) infects up to 90% of the general population. After primary infection, occurring early during childhood, a state of non-replicative infection is... (Review)
Review
Polyomavirus BK (BKV) infects up to 90% of the general population. After primary infection, occurring early during childhood, a state of non-replicative infection is established in the reno-urinary tract, without complications for immunocompetent hosts. In immunocompromised individuals, particularly transplanted patients, asymptomatic BKV viremia and/or viruria can be observed. Renal grafts may also be sources of infection as BKV prefers kidneys rather than other solid organs for transplantation such as the liver. The mechanism behind the higher incidence of BKV infection in kidney transplant patients, compared to liver or heart transplantation, is unclear and the prevalence of BKV infection in non-renal solid organ transplants has not been yet thoroughly investigated. We evaluated the prevalence of Polyomavirus BK infection among liver transplant recipients. A PubMed search was conducted using the terms BKV infection AND liver transplant recipients; BKV AND non-renal solid organ transplant*; BKV infection AND immunosuppression; the search was limited to title/abstract and English-language articles published from 2000, to March 2015. Eleven relevant studies suggest that the prevalence of BKV viruria and/or viremia among liver transplant recipients is less than that reported in kidney or heart transplant recipients, except when chronic kidney disease (CKD) is present at the same time. Data also suggest that viruric and viremic patients have higher levels of serum creatinine than BKV negative patients. Moreover, no specific immunosuppressive drugs are associated with the onset of BKV nephropathy. The comorbidity of transplantation and CKD could play a major role in promoting BKV replication.
Topics: BK Virus; Comorbidity; Humans; Immunocompromised Host; Immunosuppressive Agents; Liver Transplantation; Opportunistic Infections; Polyomavirus Infections; Prevalence; Renal Insufficiency, Chronic; Risk Factors; Treatment Outcome; Tumor Virus Infections; Virus Activation; Virus Replication
PubMed: 26819520
DOI: 10.3748/wjg.v22.i4.1532 -
Journal of Clinical Virology : the... Oct 2015BK virus (BKV) causes BKV nephritis in renal transplant patients and contributes significantly to the increase of probability of graft loss. BKV, being latent in the... (Review)
Review
BK virus (BKV) causes BKV nephritis in renal transplant patients and contributes significantly to the increase of probability of graft loss. BKV, being latent in the urogenital tract, is likely to be transported with the donor kidney to recipients and following reactivation replicates in the nucleus of renal epithelial tubular cells. BKV daughter viruses are released and enter other renal epithelial cells to spread infection. There are still a lot of unknown factors about the mechanism and kinetics of BKV infection. The treatment of BKV infection, with exception of reduction in immunosuppression which increases the risk of allograft rejection, is almost exclusively limited to application of anti-viral drugs with rather inconsistent results. The shortcomings of anti-viral therapies demand the understanding of early steps of infection of permissive cells by BK virus in hope that adequate interventional therapies preventing infection of cells with BK virus could be developed. This review describes the BKV entry in target human cells, intracellular trafficking pathways of BKV particles and potential therapeutic implications based on understanding of mechanisms of BKV infection of renal cells.
Topics: Antiviral Agents; BK Virus; Epithelial Cells; Humans; Virus Internalization
PubMed: 26295751
DOI: 10.1016/j.jcv.2015.08.003