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Journal of Infection and Public Health Jun 2011
Topics: BK Virus; Central Nervous System Infections; Humans; Polyomavirus Infections; Tumor Virus Infections; Viral Tropism
PubMed: 21663880
DOI: 10.1016/j.jiph.2011.02.002 -
Clinical & Developmental Immunology 2013JC and BK polyomaviruses were discovered over 40 years ago and have become increasingly prevalent causes of morbidity and mortality in a variety of distinct,... (Review)
Review
JC and BK polyomaviruses were discovered over 40 years ago and have become increasingly prevalent causes of morbidity and mortality in a variety of distinct, immunocompromised patient cohorts. The recent discoveries of eight new members of the Polyomaviridae family that are capable of infecting humans suggest that there are more to be discovered and raise the possibility that they may play a more significant role in human disease than previously understood. In spite of this, there remains a dearth of specific therapeutic options for human polyomavirus infections and an incomplete understanding of the relationship between the virus and the host immune system. This review summarises the human polyomaviruses with particular emphasis on pathogenesis in those directly implicated in disease aetiology and the therapeutic options available for treatment in the immunocompromised host.
Topics: Antiviral Agents; BK Virus; Genome, Viral; Humans; Immune Evasion; Immune System; Immunocompromised Host; JC Virus; Phylogeny; Polyomaviridae; Polyomavirus Infections; RNA, Viral; Tumor Virus Infections; Virus Activation
PubMed: 23737811
DOI: 10.1155/2013/373579 -
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 -
Experimental and Clinical... Jan 2019The prevalence of BK-induced nephritis in renal transplant recipients is estimated to be 1% to 10%; the rate of graft loss within 1 year is 30% to 65%. We conducted this...
OBJECTIVES
The prevalence of BK-induced nephritis in renal transplant recipients is estimated to be 1% to 10%; the rate of graft loss within 1 year is 30% to 65%. We conducted this study to evaluate screening of BK virus in blood and/or urine among renal transplant recipients and to assess the effects of different therapeutic modalities in renal transplant recipients with BK nephropathy.
MATERIALS AND METHODS
Kidney transplant recipients were screened at the time of transplant and then at 1, 2, 3, 6, 9, 12, 18, and 24 months posttransplant. Fiftynine patients were diagnosed with BK virus viremia. Patients were divided into 2 groups according to treatment: group 1 (n = 29) received an active treatment and group 2 (n = 30) received minimized immunosuppression.
RESULTS
Most patients required graft biopsies to confirm diagnosis (86.2% in group 1 vs 50% in group 2; P = .03). Both groups were comparable regarding demographic data. Initial posttransplant graft function was significantly better in group 1 (P = .017); ultimately, there was no significant difference between both groups regarding graft survival (P= .51). Fifty percent of patients had biopsy-proven acute T-cell-mediated rejection before BK virus-associated nephropathy diagnosis (significantly higher in group 1). Serum creatinine levels were significantly better in group 2 at 3, 4, and 5 years after BK nephropathy (P = .001, .017, and .003, respectively).
CONCLUSIONS
The prevalence of BK nephropathy in our renal transplant recipients was 5.9% with a rate of graft loss ranging from 43% to 51%. Regular screening, less intensive immunosuppressive therapy, and early intervention by reduction of immunosuppressive medications are advisable to obtain early diagnosis and to have better outcomes of BK virus-associated nephropathy with antiviral agents.
Topics: Antiviral Agents; BK Virus; Graft Survival; Humans; Immunosuppressive Agents; Kidney Transplantation; Kuwait; Opportunistic Infections; Polyomavirus Infections; Prevalence; Retrospective Studies; Risk Factors; Time Factors; Treatment Outcome; Tumor Virus Infections
PubMed: 30777529
DOI: 10.6002/ect.MESOT2018.O17 -
The Indian Journal of Medical Research Nov 2013Stem cell and organ transplantation are considered as the major advances of modern medicine. Unfortunately the success of transplantation is limited by its toxicity and... (Review)
Review
Stem cell and organ transplantation are considered as the major advances of modern medicine. Unfortunately the success of transplantation is limited by its toxicity and infectious complications as a result of profound immunosuppression. Viral infections are an extremely common and predictable problem in these patients. Antiviral drugs given either prophylactically or as early therapy for patients with detectable viral loads appear to be an effective strategy for reducing viral infections. However, long-term treatment with these drugs is associated with significant toxicity, expense and the appearance of drug resistant virus isolates ultimately resulting in treatment failure. Over the last few years, there is increasing evidence that cellular immune therapies can reverse the outgrowth of haematological malignancies and can also provide therapeutic benefit against lethal viral infections. While the expansion and adoptive transfer of virus-specific T-cells from the healthy donor can be an effective strategy to control viral replication, this is not possible when donors are seronegative or are subsequently inaccessible. Recent studies have demonstrated successful expansion of virus-specific T-cells from seropositive stem cell transplant recipients of a seronegative graft with active virus disease and the long term reconstitution of protective anti-viral immunity following their adoptive transfer back into the patients. Furthermore, this immunotherapeutic strategy has also been extended for multiple pathogens including cytomegalovirus, Epstein-Barr virus, adenovirus and BK polyoma-virus. This approach can be employed to rapidly expand multiple pathogens-specific T cells that can be used for adoptive immunotherapy. Finally, new assays to monitor T cell immunity have been developed which will allow to identify the high risk transplant patients who may develop virus-associated complications post-transplantation and can be given adoptive T cell therapy prophylactically.
Topics: Adenoviridae; Antiviral Agents; BK Virus; Cytomegalovirus; Herpesvirus 4, Human; Humans; Immunotherapy, Adoptive; Infections; Interferon-gamma; Organ Transplantation; Stem Cell Transplantation; T-Lymphocytes; Viral Load; Virus Diseases
PubMed: 24434332
DOI: No ID Found -
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 -
BMC Infectious Diseases Aug 2020BK virus-associated nephropathy (BKVAN) is a relatively common cause of renal dysfunction in the first six months after renal transplantation. It arises from...
BACKGROUND
BK virus-associated nephropathy (BKVAN) is a relatively common cause of renal dysfunction in the first six months after renal transplantation. It arises from reactivation of the latent and usually harmless BK virus (BK virus) due to immunosuppression and other factors including some that are unique to renal transplantation such as allograft injury. BKVAN is much rarer in non-renal solid organ transplantation, where data regarding diagnosis and management are extremely limited.
CASE PRESENTATION
We report a case of a 58-year-old man found to have worsening renal dysfunction nine months after bilateral sequential lung transplantation for chronic obstructive pulmonary disease (COPD). He had required methylprednisolone for acute allograft rejection but achieved good graft function. Urine microscopy and culture and renal ultrasound were normal. BK virus PCR was positive at high levels in urine and blood. Renal biopsy subsequently confirmed BKVAN. The patient progressed to end-stage renal failure requiring haemodialysis despite reduction in immunosuppression, including switching mycophenolate for everolimus, and the administration of intravenous immunoglobulin (IVIG).
CONCLUSIONS
This very rare case highlights the challenges presented by BK virus in the non-renal solid organ transplant population. Diagnosis can be difficult, especially given the heterogeneity with which BKV disease has been reported to present in such patients, and the optimal approach to management is unknown. Balancing reduction in immunosuppression against prevention of allograft rejection is delicate. Improved therapeutic options are clearly required.
Topics: BK Virus; DNA, Viral; Humans; Immunoglobulins, Intravenous; Immunosuppressive Agents; Kidney Transplantation; Lung Transplantation; Male; Methylprednisolone; Middle Aged; Mycophenolic Acid; Polyomavirus Infections; Pulmonary Disease, Chronic Obstructive; Tumor Virus Infections
PubMed: 32795251
DOI: 10.1186/s12879-020-05292-0 -
Experimental and Clinical... Oct 2020Alemtuzumab, a monoclonal antibody utilized as induction immunosuppression in renal transplant, targets CD52-positive lymphocytes, causing profound B- and T-cell...
OBJECTIVES
Alemtuzumab, a monoclonal antibody utilized as induction immunosuppression in renal transplant, targets CD52-positive lymphocytes, causing profound B- and T-cell depletion. The administration of such novel, potent immunosuppressive agents, with the goal of reducing rejection, poses an increased threat of BK virus infection in renal transplant recipients.
MATERIALS AND METHODS
This internal review boardapproved retrospective analysis included 676 renal transplant patients during a 9-year period. All patients were induced with alemtuzumab, and most received a steroid-minimizing regimen. BK viremia was defined as a clinically significant BK virus infection confirmed by polymerase chain reaction.
RESULTS
Of total study recipients, 58 (8.6%) were positive for BK viremia. African American race/ethnicity, age > 65 years, and rejection showed significant associations with BK viremia. Kaplan-Meier analyses demonstrated significant differences in 3-year (P = .032), 5-year (P = .025), and overall rejection (P = .031) between patients with and without BK viremia. Differences were found in overall (P = .002) and 5-year (P = .001) death-censored graft survival for patients positive for BK viremia plus another non-BK infection versus patients without BK viremia or other infection. BK viremia-positive patients with other infections had significantly lower overall (P = .010) and 5-year (P = .010) death-censored graft survival than patients with BK viremia but without other infections. When we excluded other infections, we observed no differences between BK viremia-positive and BK viremia-negative patients.
CONCLUSIONS
BK viremia incidence following alemtuzumab induction therapy appears to be comparable to that shown in other reports and slightly lower than the incidence in patients receiving non-alemtuzumab immunosuppression. BK virus may increase risk of rejection, and BK virus plus another infection may lead to decreased graft survival. African American patients, patients > 65 years old, and patients with rejection history may be at increased risk of BK virus. Closer screening should be considered in these populations.
Topics: Adult; Aged; Alemtuzumab; BK Virus; Female; Host-Pathogen Interactions; Humans; Immunocompromised Host; Immunosuppressive Agents; Incidence; Kidney Transplantation; Male; Middle Aged; Ohio; Opportunistic Infections; Polyomavirus Infections; Retrospective Studies; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome; Tumor Virus Infections
PubMed: 31324134
DOI: 10.6002/ect.2019.0041 -
Frontiers in Cellular and Infection... 2022BK polyomavirus infection results in renal allograft dysfunction, and it is important to find methods of prediction and treatment. As a regulator of host immunity,...
BACKGROUND
BK polyomavirus infection results in renal allograft dysfunction, and it is important to find methods of prediction and treatment. As a regulator of host immunity, changes in the gut microbiota are associated with a variety of infections. However, the correlation between microbiota dysbiosis and posttransplant BK polyomavirus infection was rarely studied. Thus, this study aimed to characterize the gut microbiota in BK polyomavirus-infected renal transplant recipients in order to explore the biomarkers that might be potential therapeutic targets and establish a prediction model for posttransplant BK polyomavirus infection based on the gut microbiota.
METHODS
We compared the gut microbial communities of 25 BK polyomavirus-infected renal transplant recipients with 23 characteristic-matched controls, applying the 16S ribosomal RNA gene amplicon sequencing technique.
RESULTS
At the phylum level, / ratio significantly increased in the BK polyomavirus group. was positively correlated with CD4/CD8 ratio. In the top 20 dominant genera, and exhibited a significant difference between the two groups. No significant difference was observed in microbial alpha diversity. Beta diversity revealed a significant difference between the two groups. Nine distinguishing bacterial taxa were discovered between the two groups. We established a random forest model using genus taxa to predict BK polyomavirus infectious status, which achieved the best accuracy (80.71%) with an area under the curve of 0.82. Two genera were included in the best model, which were and .
CONCLUSIONS
BK polyomavirus-infected patients had gut microbiota dysbiosis in which the / ratio increased in the course of the viral infection. Nine distinguishing bacterial taxa might be potential biomarkers of BK polyomavirus infection. The random forest model achieved an accuracy of 80.71% in predicting the BKV infectious status, with and included.
Topics: BK Virus; Biomarkers; Case-Control Studies; Dysbiosis; Gastrointestinal Microbiome; Humans; Kidney Transplantation; Polyomavirus Infections
PubMed: 35694540
DOI: 10.3389/fcimb.2022.860201 -
The Indian Journal of Medical Research Sep 2022BK virus (BKV) is a polyomavirus and cause of a common infection after renal transplantation which could be preceded to BKV-associated nephropathy. It has four main...
BACKGROUND & OBJECTIVES
BK virus (BKV) is a polyomavirus and cause of a common infection after renal transplantation which could be preceded to BKV-associated nephropathy. It has four main subtypes (I-IV). BKV subtypes II and III are rare, whereas subtype I shows a ubiquitous distribution. The objective of the present study was to investigate the prevailing BKV subtypes and subgroups in renal transplant patients in Sri Lanka.
METHODS
The presence of BKV in urine was tested through virus load quantification by real-time PCR from 227 renal transplant patients who were suspected to have BKV infection. Of these patients only 41 were found to be BKV infected (>10 copies/ml) and those were subjected to conventional PCR amplification of VP1 gene followed by BKV genotyping via phylogenetic analysis based on DNA sequencing data.
RESULTS
Persistent BK viral loads varied from 1×10 to 3×10 copies/ml. Of the 41 patient samples, 25 gave positive results for PCR amplification of subtyping region of VP1 gene of BKV. BKV genotyping resulted in detecting subtype I in 18 (72%) and subtype II in seven (28%) patients. BKV subgroups of Ia, Ib-1 and Ib-11, and Ic were identified with frequencies of 6/18 (33.3%), 6/18 (33.3%), 5/18 (27.8%), and 1/18 (5.6%), respectively.
INTERPRETATION & CONCLUSIONS
Findings from this preliminary study showed a high occurrence of subtype I, while the presence of subtype II, which is rare and less prevalent, was a novel finding for this Asian region. This emphasizes the need for further molecular and serological studies to determine the prevalence of different BKV subtypes in Sri Lanka.
Topics: Humans; BK Virus; Kidney Transplantation; Phylogeny; Sri Lanka; DNA, Viral; Tumor Virus Infections; Polyomavirus Infections; Viral Load
PubMed: 36453291
DOI: 10.4103/ijmr.IJMR_79_20