Infection of Vero Cells by BK Virus Is Dependent on Caveolae

ABSTRACT Polyomavirus-associated nephropathy occurs in ∼5% of renal transplant recipients and results in loss of graft function in 50 to 70% of these patients. The disease is caused by reactivation of the common human polyomavirus BK (BKV) in the transplanted kidney. The early events in productive BKV infection are unknown. In this report, we focus on elucidating the mechanisms of BKV internalization in its target cell. Our data reveal that BKV entry into permissive Vero cells is slow, is independent of clathrin-coated-pit assembly, is dependent on an intact caveolin-1 scaffolding domain, is sensitive to tyrosine kinase inhibition, and requires cholesterol. BKV colocalizes with the caveola-mediated endocytic marker cholera toxin subunit B but not with the clathrin-dependent endocytic marker transferrin. In addition, BKV infectious entry is sensitive to elevation in intracellular pH. These findings indicate that BKV entry into Vero cells occurs by caveola-mediated endocytosis involving a pH-dependent step.

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An N-Linked Glycoprotein with α(2,3)-Linked Sialic Acid Is a Receptor for BK Virus

Journal of Virology ◽

10.1128/jvi.79.22.14442-14445.2005 ◽

2005 ◽

Vol 79 (22) ◽

pp. 14442-14445 ◽

Cited By ~ 57

Author(s):

Aisling S. Dugan ◽

Sylvia Eash ◽

Walter J. Atwood

Keyword(s):

Sialic Acid ◽

Renal Transplant ◽

Bk Virus ◽

Human Polyomavirus ◽

Cellular Receptor ◽

Renal Transplant Recipients ◽

Critical Component ◽

Transplant Recipients ◽

Susceptibility To Infection ◽

Infection Inhibition

ABSTRACT BK virus (BKV) is a common human polyomavirus infecting >80% of the population worldwide. Infection with BKV is asymptomatic, but reactivation in renal transplant recipients can lead to polyomavirus-associated nephropathy. In this report, we show that enzymatic removal of α(2,3)-linked sialic acid from cells inhibited BKV infection. Reconstitution of asialo cells with α(2,3)-specific sialyltransferase restored susceptibility to infection. Inhibition of N-linked glycosylation with tunicamycin reduced infection, but inhibition of O-linked glycosylation did not. An O-linked-specific α(2,3)-sialyltransferase was unable to restore infection in asialo cells. Taken together, these data indicate that an N-linked glycoprotein containing α(2,3)-linked sialic acid is a critical component of the cellular receptor for BKV.

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Higher CD19+CD25+ Bregs are independently associated with better graft function in renal transplant recipients

BMC Nephrology ◽

10.1186/s12882-021-02374-2 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Eman H. Ibrahim ◽

Mostafa G. Aly ◽

Gerhard Opelz ◽

Christian Morath ◽

Martin Zeier ◽

...

Keyword(s):

Renal Transplant ◽

B Cell ◽

Graft Function ◽

Cell Subset ◽

Immunosuppressive Drugs ◽

Renal Transplant Recipients ◽

Healthy Controls ◽

Transplant Recipients ◽

Significant Positive Association ◽

Ifn Γ

Abstract Background The Identification of B cell subsets with regulatory functions might open the way to new therapeutic strategies in the field of transplantation, which aim to reduce the dose of immunosuppressive drugs and prolong the graft survival. CD25 was proposed as a marker of a B-cell subset with an immunosuppressive action termed Bregs. The effect of CD19 + CD25 + Bregs on graft function in renal transplant recipients has not yet been elucidated. We investigated a potential impact of CD19 + CD25 + Bregs on renal graft function as well as a possible interaction of CD19 + CD25 + Bregs with peripheral Tregs in healthy controls, end-stage kidney disease patients (ESKD), and renal transplant recipients. Moreover, we aimed to investigate the association of CD19 + CD25 + Bregs with serum IL-10, TGF-ß1, and IFN-γ in the same study groups. Method Thirty-one healthy controls, ninety renal transplant recipients, and eighteen ESKD patients were enrolled. We evaluated the CD19 + CD25 + Bregs and Treg absolute counts. Next, we investigated CD19 + CD25 + Bregs as predictors of good graft function in multiple regression and ROC analyses. Finally, we evaluated the association between CD19 + CD25+ Bregs and serum IL-10, TGF-ß, and IFN-γ. Results ESKD patients and renal transplant recipients showed lower counts of CD19 + CD25+ Bregs compared to healthy controls (p < 0.001). Higher CD19 + CD25+ Breg counts were independently associated with a better GFR in renal transplant recipients (unstandardized B coefficient = 9, p = 0.02). In these patients, higher CD19 + CD25+ Bregs were independently associated with higher Treg counts (unstandardized B = 2.8, p = 0.004). In ROC analysis, cut-offs for CD19 + CD25 + Breg counts and serum TGF-ß1 of 0.12 cell/μl and 19,635.4 pg/ml, respectively, were shown to provide a good sensitivity and specificity in identifying GFR ≥ 30 ml/min (AUC = 0.67, sensitivity 77%, specificity 43%; AUC = 0.65, sensitivity 81%, specificity 50%, respectively). Finally, a significant positive association between CD19 + CD25+ Bregs and TGF-ß1 was shown in renal transplant recipients (r = 0.255, p = 0.015). Conclusions Our findings indicate that higher counts of CD19 + CD25+ Bregs are independently associated with better renal function and higher absolute Treg counts in renal transplant recipients.

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Tacrolimus-Based Immunosuppressive Therapy Influences Sex Hormone Profile in Renal-Transplant Recipients—A Research Study

Biology ◽

10.3390/biology10080709 ◽

2021 ◽

Vol 10 (8) ◽

pp. 709

Author(s):

Dagmara Szypulska-Koziarska ◽

Aleksandra Wilk ◽

Małgorzata Marchelek-Myśliwiec ◽

Daria Śleboda-Taront ◽

Barbara Wiszniewska

Keyword(s):

Renal Transplant ◽

Immunosuppressive Therapy ◽

Follicle Stimulating Hormone ◽

Plasma Concentrations ◽

Graft Function ◽

Hormonal Status ◽

Renal Transplant Recipients ◽

Transplant Recipients ◽

Study Results ◽

Stimulating Hormone

It is estimated that approximately 20% of couples suffer from infertility worldwide and within renal-transplant recipients, this problem is 10 times more common. An intake of immunosuppressants may lead to hormonal imbalance. The aim of the study was to investigate the influence of tacrolimus-based therapy on the hormonal status of grafted patients. Blood samples were obtained from patients from the Department of Nephrology, Transplantology, and Internal Medicine of Independent Public Clinical Hospital No. 2, Pomeranian Medical University. All 121 patients had stable graft function for over 6 months. The blood plasma concentrations of luteinizing hormone, follicle-stimulating hormone, prolactin, testosterone, estradiol, cortisol were assessed by the electrochemiluminescence method. We observed decreased levels of prolactin (11.9 ng/mL) and cortisol (87.4 μg/mL) in patients under tacrolimus-based therapy. Tacrolimus-based therapy was also associated with increased testosterone and follicle-stimulating hormone in males, 4.04 ng/mL and 6.9 mLU/mL, respectively, and decreased testosterone levels in females, 0.121 ng/mL. We also assessed that immunosuppressive therapy based on tacrolimus is less nephrotoxic in comparison to other regimens. Concluding, tacrolimus-based therapy may influence the hormonal status of transplant recipients in the current study. Results presented here are believed to be helpful for clinicians and patients, especially within the aspect of willingness for biological offspring.

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Everolimus Conversion to Treat BK Virus Infection in Renal Transplant Recipients: Interim Analysis of a Pilot Study.

Transplantation Journal ◽

10.1097/00007890-201407151-01874 ◽

2014 ◽

Vol 98 ◽

pp. 558-559 ◽

Cited By ~ 1

Author(s):

D. Wojciechowski ◽

A. Webber ◽

S. Chandran ◽

R. Hirose ◽

F. Vincenti

Keyword(s):

Pilot Study ◽

Renal Transplant ◽

Virus Infection ◽

Interim Analysis ◽

Bk Virus ◽

Renal Transplant Recipients ◽

Transplant Recipients

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NFATC1genotypes affect acute rejection and long-term graft function in cyclosporine-treated renal transplant recipients

Pharmacogenomics ◽

10.2217/pgs-2016-0171 ◽

2017 ◽

Vol 18 (4) ◽

pp. 381-392 ◽

Cited By ~ 3

Author(s):

Qinxia Xu ◽

Xiaoyan Qiu ◽

Zheng Jiao ◽

Ming Zhang ◽

Jianping Chen ◽

...

Keyword(s):

Renal Transplant ◽

Acute Rejection ◽

Graft Function ◽

Renal Transplant Recipients ◽

Transplant Recipients

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BK Virus-Specific Antibodies and BKV DNA in Renal Transplant Recipients with BKV Nephritis

American Journal of Transplantation ◽

10.1111/j.1600-6143.2005.01080.x ◽

2005 ◽

Vol 5 (11) ◽

pp. 2719-2724 ◽

Cited By ~ 56

Author(s):

Sundaram Hariharan ◽

Eric P. Cohen ◽

Brahm Vasudev ◽

Rimas Orentas ◽

Raphael P. Viscidi ◽

...

Keyword(s):

Renal Transplant ◽

Bk Virus ◽

Renal Transplant Recipients ◽

Transplant Recipients ◽

Specific Antibodies

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BK virus replication in renal transplant recipients: Analysis of potential risk factors may contribute in reactivation

Journal of Clinical Virology ◽

10.1016/j.jcv.2017.09.004 ◽

2017 ◽

Vol 96 ◽

pp. 7-11 ◽

Cited By ~ 8

Author(s):

Mohammad Shenagari ◽

Ali Monfared ◽

Hadise Eghtedari ◽

Aydin Pourkazemi ◽

Tolou Hasandokht ◽

...

Keyword(s):

Risk Factors ◽

Renal Transplant ◽

Virus Replication ◽

Potential Risk ◽

Bk Virus ◽

Renal Transplant Recipients ◽

Transplant Recipients ◽

Potential Risk Factors

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The relationship between serum and urine NGAL and graft function in pediatric renal transplant recipients

Nefrología (English Edition) ◽

10.1016/j.nefroe.2015.08.001 ◽

2015 ◽

Vol 35 (4) ◽

pp. 419-420

Author(s):

Sepideh Hekmat ◽

Hasan Otukesh ◽

Nahid Rahimzadeh ◽

Rozita Hoseini

Keyword(s):

Renal Transplant ◽

Graft Function ◽

Renal Transplant Recipients ◽

Transplant Recipients ◽

Urine Ngal ◽

Pediatric Renal Transplant ◽

Pediatric Renal Transplant Recipients ◽

The Relationship ◽

Serum And Urine

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Effects of Rituximab on the Development of Viral and Fungal Infections in Renal Transplant Recipients

ISRN Transplantation ◽

10.5402/2013/819025 ◽

2013 ◽

Vol 2013 ◽

pp. 1-8 ◽

Cited By ~ 6

Author(s):

Samir J. Patel ◽

Jennifer M. Devos ◽

Richard J. Knight ◽

Kyle L. Dawson ◽

Wadi N. Suki ◽

...

Keyword(s):

Renal Transplant ◽

Odds Ratio ◽

Viral Infections ◽

Fungal Infections ◽

Graft Function ◽

Deceased Donor ◽

Infectious Complications ◽

Renal Transplant Recipients ◽

Transplant Recipients ◽

Kidney Transplant Recipients

Background. Rituximab is becoming increasingly utilized in renal transplant recipients; however, its association with infections remains unclear. Methods. We reviewed the incidence of viral and fungal infections in kidney transplant recipients treated with () or without () rituximab (RTX) in addition to standard immunosuppression. Results. Infections occurred in 134 (30%) patients, with a greater proportion in RTX versus no RTX patients (47% versus 28%; ). Viral infections occurred in 44% and 27% of RTX and no RTX patients, respectively (). This was largely driven by the frequency of BK viremia and noncytomegalovirus/non-BK viruses in RTX patients (27% versus 13% () and 15% versus 2% (), resp.). Fungal infections also occurred more often in RTX patients (11% versus 3 %; ). Multivariate analysis revealed deceased donor recipient (odds ratio = 2.5; ) and rituximab exposure (odds ratio = 2.2; ) as independent risk factors for infection. Older patients, deceased donor recipients, those on dialysis longer, and those with delayed graft function tended to be at a greater risk for infections following rituximab. Conclusions. Rituximab is associated with an increased incidence of viral and fungal infections in kidney transplantation. Additional preventative measures and/or monitoring infectious complications may be warranted in those receiving rituximab.

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