BK Polyomavirus Subtypes IVc-1 and Ib-1 in Vietnamese Renal Transplant Recipients.
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ABSTRACT:
SUBMITTER: Dinh HTT
PROVIDER: S-EPMC8388545 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Symptomatic BK polyomavirus (BKPyV) infections are common and relevant in immunocompromised patients. Here, we present full-length BKPyV genomes from samples from patients who received hematopoietic cell transplants in the United States. These individuals had non-subtype I BKPyV, as determined by amplification, next-generation sequencing, and phylogenetic analysis.
| S-EPMC8759406 | biostudies-literature
Project description:BackgroundBK 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.MethodsWe 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.ResultsAt the phylum level, Firmicutes/Bacteroidetes ratio significantly increased in the BK polyomavirus group. Bacteroidetes was positively correlated with CD4/CD8 ratio. In the top 20 dominant genera, Romboutsia and Roseburia 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 Romboutsia and Actinomyces.ConclusionsBK polyomavirus-infected patients had gut microbiota dysbiosis in which the Firmicutes/Bacteroidetes 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 Romboutsia and Actinomyces included.
| S-EPMC9186314 | biostudies-literature
Project description:BK polyomavirus (BKV or BKPyV) associated nephropathy affects up to 10% of kidney transplant recipients (KTRs). BKV isolates are categorized into four genotypes. It is currently unclear whether the four genotypes are also serotypes. To address this issue, we developed high-throughput serological assays based on antibody-mediated neutralization of BKV genotype I and IV reporter vectors (pseudoviruses). Neutralization-based testing of sera from mice immunized with BKV-I or BKV-IV virus-like particles (VLPs) or sera from naturally infected human subjects revealed that BKV-I specific serum antibodies are poorly neutralizing against BKV-IV and vice versa. The fact that BKV-I and BKV-IV are distinct serotypes was less evident in traditional VLP-based ELISAs. BKV-I and BKV-IV neutralization assays were used to examine BKV type-specific neutralizing antibody responses in KTRs at various time points after transplantation. At study entry, sera from 5% and 49% of KTRs showed no detectable neutralizing activity for BKV-I or BKV-IV neutralization, respectively. By one year after transplantation, all KTRs were neutralization seropositive for BKV-I, and 43% of the initially BKV-IV seronegative subjects showed evidence of acute seroconversion for BKV-IV neutralization. The results suggest a model in which BKV-IV-specific seroconversion reflects a de novo BKV-IV infection in KTRs who initially lack protective antibody responses capable of neutralizing genotype IV BKVs. If this model is correct, it suggests that pre-vaccinating prospective KTRs with a multivalent VLP-based vaccine against all BKV serotypes, or administration of BKV-neutralizing antibodies, might offer protection against graft loss or dysfunction due to BKV associated nephropathy.
| S-EPMC3325208 | biostudies-literature
Project description:JC polyomavirus (JCPyV) may cause clinical syndromes such as progressive multifocal leukoencephalopathy in immunocompromised patients. Here, we report seven complete genome sequences of JCPyV genotype 7A, generated directly from urine samples from Vietnamese renal transplant recipients by using rolling-circle amplification and next-generation sequencing.
| S-EPMC6952662 | biostudies-literature
Project description:Background and objectivesBK polyomavirus (BKV) infection commonly complicates kidney transplantation, contributing to morbidity and allograft failure. The virus is often donor-derived and influenced by ischemia-reperfusion processes and disruption of structural allograft integrity. We hypothesized that deceased-donor AKI associates with BKV infection in recipients.Design, setting, participants, & measurementsWe studied 1025 kidney recipients from 801 deceased donors transplanted between 2010 and 2013, at 13 academic centers. We fitted Cox proportional-hazards models for BKV DNAemia (detectable in recipient blood by clinical PCR testing) within 1 year post-transplantation, adjusting for donor AKI and other donor- and recipient-related factors. We validated findings from this prospective cohort with analyses for graft failure attributed to BKV within the Organ Procurement and Transplantation Network (OPTN) database.ResultsThe multicenter cohort mean kidney donor profile index was 49±27%, and 26% of donors had AKI. Mean recipient age was 54±13 years, and 25% developed BKV DNAemia. Donor AKI was associated with lower risk for BKV DNAemia (adjusted hazard ratio, 0.53; 95% confidence interval, 0.36 to 0.79). In the OPTN database, 22,537 (25%) patients received donor AKI kidneys, and 272 (0.3%) developed graft failure from BKV. The adjusted hazard ratio for the outcome with donor AKI was 0.7 (95% confidence interval, 0.52 to 0.95).ConclusionsIn a well-characterized, multicenter cohort, contrary to our hypothesis, deceased-donor AKI independently associated with lower risk for BKV DNAemia. Within the OPTN database, donor AKI was also associated with lower risk for graft failure attributed to BKV.PodcastThis article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2021_03_10_CJN18101120_final.mp3.
| S-EPMC8259491 | biostudies-literature
Project description:BackgroundThe immunosuppressive agents mycophenolate acid (MPA) and tacrolimus (Tac) are associated with a higher incidence of BK polyomavirus nephropathy (BKPyVAN). In this observational retrospective cohort study, the frequency of BK polyomavirus (BKPyV) complications over a 24-month period was studied.Methods358 renal transplant recipients (RTR) treated with MPA, with either cyclosporine A (CsA) (CsAM group) or Tac (TacM group) and mostly prednisolone, were included.ResultsIncidence of BKPyV-viremia was not significantly different between the CsAM (n = 42/191) (22.0%) and the TacM (n = 36/167) (21.6%) group. Biopsy proven BKPyVAN occurred more often in the TacM group (6.6%) versus the CsAM group (2.1%) (p = 0.03). Longitudinal data analysis showed a significant earlier decline of viral load in plasma in the CsAM group compared to the TacM group (p = 0.005). The incidence of biopsy proven acute rejection (BPAR) was significantly higher in the CsAM (19.9%) compared to the TacM (10.8%) (p = 0.02) group. Graft loss, estimated glomerular filtration rate and mortality rate did not differ in both treatment groups.ConclusionIn conclusion, this study shows that immunosuppressive treatment with Tac and MPA compared to CsA and MPA is associated with a lower incidence of BPAR, but at the cost of an increased risk of developing BKPyVAN in the first two years post-transplant.
| S-EPMC5469458 | biostudies-literature
Project description:BackgroundMerkel cell carcinoma (MCC) is a rare skin cancer associated with immunosuppression and the integration of Merkel cell polyomavirus (MCPyV) DNA into the tumor cell genome. Little is known about the natural history of MCPyV infection.ObjectivesTo investigate the presence of MCPyV, BK and JC polyomaviruses in serum and urine from immunosuppressed kidney transplant patients (KTx) and a control group of normal volunteers.Study designQuantitative real-time PCR (q-PCR) was used to assess MCPyV, BKV and JCV viral load in urine and serum samples collected from normal donors (Group A), prospectively enrolled KTx patients (Group B) and from KTx with documented BK reactivation and/or nephropathy (Group C).ResultsLow levels of MCPyV viruria was seen in 15% of the subjects in Group A, 30% of Group B, and was not detected in Group C. No individuals in the study developed MCPyV viremia. BK viruria was seen in 5% of Group A, 30% of Group B, and 100% of Group C. Consistent with previous reports, the mean BKV urinary load was significantly higher in immunosuppressed patients compared to non-immunosuppressed controls and also higher in urine compared to serum samples.ConclusionsLike BKV and JCV, MCPyV is likely a common infection in adult humans. Low level shedding of MCPyV in urine was similar in immunosuppressed organ transplant recipients to non-immunosuppressed subjects. However, MCPyV was not detected and JCV was infrequent in samples from KTx patients with clinical BKV reactivation.
| S-EPMC2943003 | biostudies-literature
Project description:BK polyomavirus (BKPyV) reactivation in kidney transplant recipients can lead to allograft damage and loss. The elements of the adaptive immune system that are permissive of reactivation and responsible for viral control remain incompletely described. We performed a prospective study evaluating BKPyV-specific T-cell response, humoral response and overall T-cell phenotype beginning pre-transplant through one year post-transplant in 28 patients at two centers. We performed an exploratory analysis of risk factors for the development of viremia and viruria as well as compared the immune response to BKPyV in these groups and those who remained BK negative. 6 patients developed viruria and 3 developed viremia. BKPyV-specific CD8+ T-cells increased post-transplant in viremic and viruric but not BK negative patients. BKPyV-specific CD4+ T-cells increased in viremic, but not viruric or BK negative patients. Anti-BKPyV IgG antibodies increased in viruric and viremic patients but remained unchanged in BK negative patients. Viremic patients had a greater proportion of CD8+ effector cells pre-transplant and at 12 months post-transplant. Viremic patients had fewer CD4+ effector memory cells at 3 months post-transplant. Exploratory analysis demonstrated lower CD4 and higher total CD8 proportions, higher anti-BKPyV antibody titers and the cause of renal failure were associated BKPyV reactivation. In conclusion, low CD4, high CD8 and increased effector CD8 cells were found pre-transplant in patients who became viremic, a phenotype associated with immune senescence. This pre-transplant T-cell senescence phenotype could potentially be used to identify patients at increased risk of BKPyV reactivation.
| S-EPMC5451008 | biostudies-literature
Project description:Kidney transplant recipients (KTRs) are exposed to a high risk of BK polyomavirus (BKPyV) replication, which in turn may lead to graft loss. Although the microRNAs (miRNAs) bkv-miR-B1-3p and bkv-miR-B1-5p are produced during the viral cycle, their putative value as markers of viral replication has yet to be established. In KTRs, the clinical relevance of the changes over time in BKPyV miRNA levels has not been determined. In a retrospective study, we analyzed 186 urine samples and 120 plasma samples collected from 67 KTRs during the first year post-transplantation. Using a reproducible, standardized, quantitative RT-PCR assay, we measured the levels of bkv-miR-B1-3p and bkv-miR-B1-5p (relative to the BKPyV DNA load). Detection of the two miRNAs had low diagnostic value for identifying patients with DNAemia or for predicting DNAuria during follow-up. Seven of the 14 KTRs with a sustained BKPyV infection within the first year post-transplantation showed a progressive reduction in the DNA load and then a rapid disappearance of the miRNAs. DNA and miRNA loads were stable in the other seven KTRs. After the DNA-based diagnosis of BKPyV infection in KTRs, bkv-miR-B1-3p and bkv-miR-B1-5p levels in the urine might be valuable markers for viral replication monitoring and thus might help physicians to avoid an excessive reduction in the immunosuppressive regimen.
| S-EPMC7926448 | biostudies-literature
Project description:BK virus (BKV) is a polyomavirus that cause of allograft dysfunction among kidney transplant recipients. The role of BKV infection in non-renal solid organ transplant recipients is not well understood neither for the relationship between various BKV strains with occurrence of BKV viral viruria. This study aimed to understand the prevalence of BKV infection and identified of BKV various strains in the urine of liver transplant recipients. There was not significant difference of renal outcome between high BKV viruria and low BKV viruria in the liver transplant recipients. The WW-non-coding control region (NCCR) BKV detected in urine was associated with higher urinary BKV load, whereas the Dunlop-NCCR BKV was detected in the urine of low urinary BKV load. An in vitro cultivation system demonstrated that WW-BKV strain exhibiting the higher viral DNA replication efficiency and higher BKV load. Altogether, this is the first study to demonstrate the impact of BKV strains on the occurrence of BK viruria in the liver transplant recipients.
| S-EPMC4919687 | biostudies-literature