scholarly journals Agnoprotein is an Essential Egress Factor during BK Polyomavirus Infection

2018 ◽  
Author(s):  
Margarita Maria-Panou ◽  
Emma L. Prescott ◽  
Daniel L. Hurdiss ◽  
Gemma Swinscoe ◽  
Michael Hollinshead ◽  
...  
Keyword(s):  
Bk Virus ◽  
Host Cells ◽  
Transplant Recipients ◽  
Wild Type ◽  
Kidney Transplant Recipients ◽  
Nuclear Egress ◽  
Virion Release ◽  
Bk Polyomavirus ◽  
Sirna Knockdown ◽  
Late Region

BK polyomavirus (BKPyV) causes a lifelong chronic infection and is associated with debilitating disease in kidney transplant recipients. Despite its importance, aspects of the virus life cycle remain poorly understood. In addition to the structural proteins, the late region of the BK genome encodes for an auxiliary protein called agnoprotein. Studies on other polyomavirus agnoproteins have suggested that the protein may contribute to virion infectivity. Here, we demonstrate an essential role for agnoprotein in BK virus release. Viruses lacking agnoprotein do not propagate to wild-type levels and fail to release from host cells. Despite this, loss of agnoprotein does not impair virion infectivity or morphogenesis. Instead, agnoprotein expression correlates with nuclear egress of BK virions. We demonstrate that the agnoprotein binding partner α-SNAP is necessary for BK virion release, and siRNA knockdown of α-SNAP prevents nuclear release of wild-type BK virions. These data highlight a novel role for agnoprotein and begin to reveal the mechanism by which polyomaviruses leave an infected cell.

scholarly journals Adjuvant Ciprofloxacin for Persistent BK Polyomavirus Infection in Kidney Transplant Recipients

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
David Arroyo ◽  
Sindhu Chandran ◽  
Parsia A. Vagefi ◽  
David Wojciechowski
Keyword(s):  
Kidney Transplant ◽  
Randomized Trials ◽  
Bk Virus ◽  
Common Complication ◽  
Transplant Recipients ◽  
Retrospective Evaluation ◽  
Kidney Transplant Recipients ◽  
Serious Adverse Events ◽  
Initial Reduction ◽  
Bk Polyomavirus

Background. BK virus (BKV) infection is a common complication following kidney transplantation. Immunosuppression reduction is the cornerstone of treatment while adjuvant drugs have been tried in small uncontrolled studies. We sought to examine our center’s experience with the use of ciprofloxacin in patients with persistent BKV infection.Methods. Retrospective evaluation of the effect of a 30-day ciprofloxacin course (250 mg twice daily) on BKV infection in kidney transplant recipients who had been diagnosed with BK viruria ≥106 copies/mL and viremia ≥500 copies/mL and in whom the infection did not resolve after immunosuppression reduction and/or treatment with other adjuvant agents. BKV in plasma and urine was evaluated after 3 months following treatment with ciprofloxacin.Results. Nine kidney transplant recipients received ciprofloxacin at a median of 130 days following the initial reduction in immunosuppression. Three patients showed complete viral clearance and another 3 had a ≥50% decrease in plasma viral load. No serious adverse events secondary to ciprofloxacin were reported and no grafts were lost due to BKV up to 1 year after treatment.Conclusion.Ciprofloxacin may be a useful therapy for persistent BKV infection despite conventional treatment. Randomized trials are required to evaluate the potential benefit of this adjuvant therapy.

#77: Impact of Targeted Tacrolimus Levels on BK Polyomavirus DNAemia Among Pediatric Kidney Transplant Recipients

2021 ◽  
Vol 10 (Supplement_1) ◽  
pp. S4-S4
Author(s):  
I Yildirim ◽  
R Liverman ◽  
S Serluco ◽  
R George ◽  
R Garro ◽  
...  
Keyword(s):  
Kidney Transplant ◽  
Early Onset ◽  
Bk Virus ◽  
First Year ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Post Intervention ◽  
Post Transplant ◽  
Bk Polyomavirus ◽  
The Impact

Abstract Background Uncontrolled BK Polyomavirus (BK) DNAemia in kidney transplant recipients is a significant cause of allograft dysfunction that can lead to BK Polyomavirus-associated nephropathy with permanent damage and graft loss. BK virus DNAemia can occur early (within the first year) or late (after the first year) following a kidney transplant in children. Prospective monitoring for BK viremia with pre-emptive lowering of immunosuppression has been suggested as an effective approach to prevent BK nephropathy. We evaluated the impact of changes in targeted tacrolimus levels on the incidence of BK DNAemia early post-transplant. Methods In response to a cluster of early-onset BK virus DNAemia cases in the first quarter of 2015, we pursued a quality improvement study to determine whether changes to tacrolimus trough targets for the first 100 days post-transplant would reduce the incidence and severity of BK DNAemia. Targeted tacrolimus levels were decreased by approximately 25% (see Table) and patients receiving transplant from March 20, 2015, and December 31, 2018, were prospectively monitored. The incidence rates of BK DNAemia detected on monthly surveillance testing in the first-year post-transplant were compared for patients transplanted between January 1, 2013, and March 14, 2015 (pre-intervention) and March 15, 2015, to December 31, 2018 (post-intervention). Results Of 148 children who received kidney transplants during the study period, 52 (35%) were transplanted in the pre-intervention era and 96(65%) were transplanted during the post-intervention era. The median age at transplant was 13.9 years [interquartile range (IQR) 8.0–16.7 years]. Age at transplant, gender (overall 55% male), and race (overall 54% White, 35% Black) was not significantly different between the cohorts. The risk of early-onset BK DNAemia within the first 100 days post-transplant was 19 per 100 patients in the pre-intervention cohort and 13 per 100 patients in the post-intervention cohort, corresponding to a 35% reduction after lowering targeted tacrolimus levels. The median time to first detected BK DNAemia increased from 77 days (IQR 45–90 days) in pre-intervention to 104 days (IQR 47–174 days) in the post-intervention cohort. Conclusions BK DNAemia heralds a serious complication of kidney transplantation and may represent over immunosuppression and increased risk for other infectious complications. We were able to reduce the rate of early-onset BK DNAemia by reducing tacrolimus target levels in the first 12 weeks post-transplant. Preventing early uncontrolled viremia may decrease the need for immunosuppression reduction which increases the risk for rejection.

scholarly journals BK Polyomavirus Micro-RNAs: Time Course and Clinical Relevance in Kidney Transplant Recipients

Viruses ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 351
Author(s):  
Baptiste Demey ◽  
Véronique Descamps ◽  
Claire Presne ◽  
Francois Helle ◽  
Catherine Francois ◽  
...  
Keyword(s):  
Viral Replication ◽  
Kidney Transplant ◽  
Clinical Relevance ◽  
Graft Loss ◽  
First Year ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Post Transplantation ◽  
Bk Polyomavirus ◽  
Micro Rnas

Background: 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. Methods: 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). Results: 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. Conclusions: 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.

BK polyomavirus viremia and antibody responses of pediatric kidney transplant recipients in Finland

2018 ◽  
Vol 23 (1) ◽  
pp. e13324 ◽  
Author(s):  
Jenni Miettinen ◽  
Irmeli Lautenschlager ◽  
Fabian Weissbach ◽  
Marion Wernli ◽  
Eeva Auvinen ◽  
...  
Keyword(s):  
Kidney Transplant ◽  
Antibody Responses ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Bk Polyomavirus

scholarly journals P1762THE EFFECT OF IMMUNOSUPPRESSIVE THERAPY ON THE CLINICAL FOLLOW-UP OF BK VIRUS IN KIDNEY TRANSPLANT RECIPIENTS

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Gulay Yilmaz ◽  
Volkan Polatkan ◽  
Ebru Ozdemir ◽  
Turker Erturk ◽  
Emel Tatli ◽  
...  
Keyword(s):  
Immunosuppressive Therapy ◽  
Kidney Transplant ◽  
Antiviral Treatment ◽  
Immunosuppressive Treatment ◽  
Bk Virus ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Group I ◽  
The Mean

Abstract Background and Aims BK virus nephropathy occurs in up to 10% of kidney transplant recipients and can result in graft loss. The reactivation of BK virus is largely asymptomatic, and routine surveillance especially in the first 12-24 months after transplant is necessary for early recognition and intervention. Reduced immunosuppression and antiviral treatment in the early stages may be effective in stopping BK virus replication. This study is designed to investigate the effect of management in immunosuppressive therapy on BK virus titers and graft functions in our kidney transplant group. Method A total of 370 kidney transplant recipients between the ages of 18-69 years and receiving a triple immunosuppressive therapy (Tacrolimus+Mycophenoloic Acid+Prednisolone) were included in the study. Demographic characteristics, BK virus titers, serum creatinine and immunosuppressive drug (Tacrolimus, Everolimus) levels were measured at regular intervals in the first 24 months. Among these patients 43 of them were found to have BK virus positivity. At the time of the detection of BK virus positivity, patients were divided into three groups regarding the change in the immunosuppressive protocols: Group I: Tacrolimus + Everolimus + Prednisolone, Group II: Everolimus + Prednisolone, Group III: Tacrolimus + Prednisolone. BK virus titers and graft functions of all three groups were compared with each other. SPSS 15 for Windows was used for statistical analysis. Results The mean age of the patients was 45.3 years, and the mean duration of transplantation was 16.3 months at the time of the BK virus positivity. During the follow-up, mean Tacrolimus levels were found to be in their highest value (14.1 ng/mL) in the posttransplant three months while BK virus titer reached the highest value (1.1x106 copies/ml) in the posttransplant seven to nine months. Increased creatinine values two months after BK virus positivity were strongly correlated (p = 0.02, p = 0.008, p = 0.05, p = 0.002 at 6th, 9th, 12th and 24th months, respectively). A significant decrease in BK virus titers was observed in all three groups due to reductions in immunosuppressive treatment protocol (p = 0.005, p = 0.003, p = 0.028, in groups I, II, III respectively). Conclusion Our study favors the benefits of the prospective screening for BK virus to identify early viral replication, permit intervention, and prevent progression to nephropathy or allograft loss. The best studied treatment for BK viremia and nephropathy is careful reduction of immunosuppression

Clinical utility of leflunomide for BK polyomavirus associated nephropathy in kidney transplant recipients: A multicenter retrospective study

2019 ◽  
Vol 21 (2) ◽  
pp. e13058 ◽  
Author(s):  
Nicolas Keller ◽  
Simon Duquennoy ◽  
Anne Conrad ◽  
Samira Fafi‐Kremer ◽  
Emmanuel Morelon ◽  
...  
Keyword(s):  
Retrospective Study ◽  
Kidney Transplant ◽  
Clinical Utility ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Bk Polyomavirus

Role of the Early Association of a mTOR Inhibitor and Tacrolimus in BK Polyomavirus Infection in Kidney Transplant Recipients

2018 ◽  
Vol 102 ◽  
pp. S566
Author(s):  
Veronica Lopéz ◽  
Teresa Vazquez ◽  
Cristina Jironda ◽  
Mercedes Cabello ◽  
Juana Alonso ◽  
...  
Keyword(s):  
Kidney Transplant ◽  
Mtor Inhibitor ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Bk Polyomavirus
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