-
Journal of the American Society of... May 2011BK and JC polyomaviruses can reactivate after transplantation, causing renal dysfunction and graft loss. The incidence of JC reactivation after renal transplant is not...
BK and JC polyomaviruses can reactivate after transplantation, causing renal dysfunction and graft loss. The incidence of JC reactivation after renal transplant is not well understood. Here, we characterized JC reactivation using samples collected during the first year after transplantation from 200 kidney recipients. We detected BK and JC viruses in the urine of 35 and 16% of transplant recipients, respectively. The median viral load in the urine was 400 times higher for BK virus than JC virus. The presence of BK viruria made concurrent JC viruria less likely: JC viruria was detected in 22% of non-BK viruric recipients compared with 4% of BK viruric recipients (P=0.001). The co-detection rate was 1.5%, which is less than the expected 5.6% if reactivation of each virus was independent (P=0.001). We did not observe JC viremia, JC nephropathy, or progressive multifocal leukoencephalopathy. The onset of JC viruria was associated with donor, but not recipient, JC-specific antibody in a titer-dependent fashion and inversely associated with donor and recipient BK-specific antibody. Donor and recipient JC seropositivity did not predict BK viruria or viremia. In conclusion, among renal transplant recipients, infection with one polyomavirus inversely associates with infection with the other.
Topics: Antibodies, Viral; BK Virus; Graft Rejection; Humans; JC Virus; Kidney Transplantation; Tissue Donors; Viral Load; Virus Activation
PubMed: 21511831
DOI: 10.1681/ASN.2010080877 -
Annals of Transplantation May 2018Human BK polyomavirus (BKV) infection is poorly documented in heart and lung transplant patients. BK viruria and viremia have been estimated to affect 19% and 5% of... (Review)
Review
Human BK polyomavirus (BKV) infection is poorly documented in heart and lung transplant patients. BK viruria and viremia have been estimated to affect 19% and 5% of heart transplant recipients, respectively. Data are limited, especially for lung transplantation, but the proportion of patients progressing from BK viruria to viremia or BKV-related nephropathy (BKVN) appears lower than in kidney transplantation. Nevertheless, a number of cases of BKVN have been reported in heart and lung transplant patients, typically with late diagnosis and generally poor outcomes. Risk factors for BKV infection or BKVN in this setting are unclear but may include cytomegalovirus infection and anti-rejection treatment. The relative infrequency of BKVN or other BK-related complications means that routine BKV surveillance in thoracic transplantation is not warranted, but a diagnostic workup for BKV infection may be justified for progressive renal dysfunction with no readily-identifiable cause; after anti-rejection therapy; and for renal dysfunction in patients with cytomegalovirus infection or hypogammaglobulinemia. Treatment strategies in heart or lung transplant recipients rely on protocols developed in kidney transplantation, with reductions in immunosuppression tailored to match the higher risk status of thoracic transplant patients.
Topics: BK Virus; Female; Heart Transplantation; Humans; Kidney Transplantation; Lung Transplantation; Male; Polyomavirus Infections; Risk Factors; TOR Serine-Threonine Kinases; Tumor Virus Infections; Viremia
PubMed: 29748530
DOI: 10.12659/AOT.908429 -
Journal of the American Society of... Jan 2018BK virus-associated nephropathy (BKVAN) causes renal allograft dysfunction. The current management of BKVAN relies on pre-emptive adaptation of immunosuppression...
BK virus-associated nephropathy (BKVAN) causes renal allograft dysfunction. The current management of BKVAN relies on pre-emptive adaptation of immunosuppression according to viral load monitoring. However, this empiric strategy is not always successful. Therefore, pretransplant predictive markers are needed. In a prospective longitudinal study, we enrolled 168 kidney transplant recipients and 69 matched donors. To assess the value of BKV genotype-specific neutralizing antibody (NAb) titers as a predictive marker for BKV replication, we measured BKV DNA load and NAb titers at transplant and followed patients for 24 months. After transplant, 52 (31%) patients displayed BKV replication: 24 (46%) patients were viruric and 28 (54%) patients were viremic, including 13 with biopsy-confirmed BKVAN. At any time, patients with high NAb titers against the replicating strain had a lower risk of developing BKV viremia (hazard ratio [HR], 0.44; 95% confidence interval [95% CI], 0.26 to 0.73; =0.002). Each log increase in NAb titer decreased the risk of developing viremia by 56%. Replicating strains were consistent with donor transmission in 95% of cases of early BKV replication. Genotype mismatch between recipients' neutralization profiles before transplant and their subsequently replicating strain significantly increased the risk of developing viremia (HR, 2.27; 95% CI, 1.06 to 4.88; =0.04). A NAb titer against the donor's strain <4 log before transplant significantly associated with BKV replication after transplant (HR, 1.88; 95% CI, 1.06 to 3.45; =0.03). BKV genotype-specific NAb titers may be a meaningful predictive marker that allows patient stratification by BKV disease risk before and after transplant.
Topics: Adolescent; Adult; Aged; Allografts; Antibodies, Neutralizing; BK Virus; DNA, Viral; Female; Genotype; Humans; Kidney Diseases; Kidney Transplantation; Longitudinal Studies; Male; Middle Aged; Polyomavirus Infections; Prospective Studies; Risk Assessment; Tumor Virus Infections; Urine; Viral Load; Viremia; Virus Replication; Young Adult
PubMed: 29042457
DOI: 10.1681/ASN.2017050532 -
American Journal of Transplantation :... Sep 2019
Topics: BK Virus; Cytomegalovirus; Cytomegalovirus Infections; Humans; Polyomavirus Infections; Viremia
PubMed: 31306544
DOI: 10.1111/ajt.15531 -
Experimental and Clinical... Feb 2018It has been hypothesized that BK polyomavirus infection leads to nephropathy in kidney transplant patients via various plausible mechanisms, such as stimulation of...
OBJECTIVES
It has been hypothesized that BK polyomavirus infection leads to nephropathy in kidney transplant patients via various plausible mechanisms, such as stimulation of chemokines. The CXCL11 gene may also play a role in BK polyomavirus-associated nephropathy. Our aim was to compare expression levels of CXCL11 in BK polyomavirus-infected versus noninfected kidney transplant patients with nephropathy and healthy controls.
MATERIALS AND METHODS
We performed a cross-sectional study of 58 kidney transplant patients with the risk of BK polyomavirus infection; these patients were subgrouped as BK polyomavirus-infected (23 patients) and noninfected (35 patients). We also enrolled 30 healthy patients as controls in this study. The BK polyomavirus genome load was evaluated using a quantitative real-time polymerase chain reaction protocol in kidney transplant patients. We analyzed CXCL11 gene expression and protein levels using in-house SYBR green real-time polymerase chain reaction and enzyme-linked immunosorbent assay protocols.
RESULTS
The expression level of the CXCL11 gene was increased 22.37 ± 23.1-fold in BK polyomavirus-infected kidney recipients and 12 ± 24-fold in noninfected patients versus that shown in controls.
CONCLUSION
From these results, we concluded that BK polyomavirus infection can induce CXCL11 gene expression in kidney transplant patients compared with that shown in patients without BK infection and healthy patients. However, further studies are needed to determine the accurate counteraction between BK polyomavirus infection and CXCL11 in kidney transplant patients.
Topics: BK Virus; Case-Control Studies; Chemokine CXCL11; Cross-Sectional Studies; Host-Pathogen Interactions; Humans; Kidney Transplantation; Peripheral Blood Stem Cells; Polyomavirus Infections; RNA, Messenger; Treatment Outcome; Tumor Virus Infections; Up-Regulation; Viral Load
PubMed: 27759557
DOI: 10.6002/ect.2015.0361 -
Journal of the American Society of... May 2018
Topics: Antibodies, Neutralizing; BK Virus; Humans; Polyomavirus; Polyomavirus Infections
PubMed: 29467142
DOI: 10.1681/ASN.2018010027 -
Journal of Clinical Virology : the... Apr 2010Polyoma viruses are ubiquitous infecting many different mammalian species including humans. There are five known human polyoma viruses. JC virus and BK virus are two... (Review)
Review
Polyoma viruses are ubiquitous infecting many different mammalian species including humans. There are five known human polyoma viruses. JC virus and BK virus are two polyoma viruses identified nearly three decades ago. Recently WU, KI and Merkel cell polyoma viruses have been isolated from humans. The exact role of these three newly discovered viruses in human disease is not known. Most human polyoma disease is caused by BK and JC viruses which are usually acquired in childhood. Approximately 50-80% of humans have seropositivity to these viruses. Clinically apparent diseases in immunocompetent hosts are extremely rare. These viruses remain latent possibly in the lymphoid organs, neuronal tissue, and kidney and under the circumstances of severe immunosuppression both these viruses reactivate. Neurotropic JC virus reaches the brain and causes progressive multifocal leukoencephalopathy, a demyelinating disease of the central nervous system with a high mortality rate. BK virus is urotheliotropic and its reactivation causes a form of interstitial nephritis, known as BK or polyoma virus associated nephropathy which is associated with high graft loss if not recognized early. There are no known effective antiviral agents for any of the polyoma viruses.
Topics: BK Virus; Humans; Immunocompromised Host; JC Virus; Polyomavirus Infections; Tumor Virus Infections; Viral Tropism; Virus Activation; Virus Latency
PubMed: 20060360
DOI: 10.1016/j.jcv.2009.12.006 -
Journal of Virology Mar 2023Polyomavirus small T antigen (tAg) plays important roles in regulating viral replication, the innate immune response, apoptosis, and transformation for SV40, Merkel cell...
Polyomavirus small T antigen (tAg) plays important roles in regulating viral replication, the innate immune response, apoptosis, and transformation for SV40, Merkel cell polyomavirus (MCPyV), murine polyomavirus (MuPyV), and JC polyomavirus (JCPyV). However, the function of BK polyomavirus (BKPyV) tAg has been much less studied. Here, we constructed mutant viruses that do not express tAg, and we showed that, in contrast with other polyomaviruses, BKPyV tAg inhibits large T antigen (TAg) gene expression and viral DNA replication. However, this occurs only in an archetype viral background. We also observed that the transduction of cells with a lentivirus-expressing BKPyV tAg kills the cells. We further discovered that BKPyV tAg interacts not only with PP2A A and C subunits, as has been demonstrated for other polyomavirus tAg proteins, but also with PP2A B''' subunit members. Knocking down either of two B''' subunits, namely STRN or STRN3, mimics the phenotype of the tAg mutant virus. However, a virus containing a point mutation in the PP2A binding domain of tAg only partially affected virus TAg expression and DNA replication. These results indicate that BKPyV tAg downregulates viral gene expression and DNA replication and that this occurs in part through interactions with PP2A. BK polyomavirus is a virus that establishes a lifelong infection of the majority of people. The infection usually does not cause any clinical symptoms, but, in transplant recipients whose immune systems have been suppressed, unchecked virus replication can cause severe disease. In this study, we show that a viral protein called small T antigen is one of the ways that the virus can persist without high levels of replication. Understanding which factors control viral replication enhances our knowledge of the virus life cycle and could lead to potential interventions for these patients.
Topics: Animals; Mice; Antigens, Viral, Tumor; BK Virus; DNA Replication; DNA, Viral; Polyomavirus Infections; Virus Replication
PubMed: 36916919
DOI: 10.1128/jvi.00077-23 -
Kidney International Feb 2006BK viremia and nephritis are increasing problems in renal transplant recipients. The exact cause of the increasing prevalence of this condition remains poorly... (Review)
Review
BK viremia and nephritis are increasing problems in renal transplant recipients. The exact cause of the increasing prevalence of this condition remains poorly understood. Increasing prevalence has been correlated with newer immunosuppressive agents and the decline in acute rejection rates in recent years. The clinical manifestation varies from the asymptomatic state of viremia and nephritis to clinical renal dysfunction. The diagnosis of this infection is based on the combination of the presence of urinary decoy cells, virus in the urine/blood, and typical renal histological findings of interstitial nephritis. Routine post-transplant screening for BK viremia and viruria prior to the occurrence of nephritis and the reduction in immunosuppressive therapy for subjects with viremia appear to be attractive approaches. The treatment of BKV nephritis (BKVN) consists of reduction in immunosuppressive therapy and antiviral therapy with cidofovir or leflunomide or a combination of both. Approximately 30-60% of subjects with BKVN experienced irreversible graft failure. However, in recent years, the combinations of early detection, prompt diagnosis, and appropriate reduction in immunosuppressive therapy have been associated with better outcome. The pathogenesis of BK virus infection in renal transplant recipients needs to be explored. The source of BKV infection (donor as opposed to recipient), the role of host humoral, and cellular immunity to BKV, and the role of alloimmune activation in renal graft to the occurrence of nephritis are discussed in this review.
Topics: Antibodies, Viral; Antiviral Agents; BK Virus; Cidofovir; Cytosine; DNA, Viral; Graft Survival; Humans; Immunity, Cellular; Immunosuppressive Agents; Isoxazoles; Kidney; Kidney Transplantation; Leflunomide; Nephritis; Organophosphonates; Polyomavirus Infections; Prevalence; Risk Factors; Treatment Outcome; Tumor Virus Infections; Viremia
PubMed: 16395271
DOI: 10.1038/sj.ki.5000040 -
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