Molecular Networks Involved in the Immune Control of BK Polyomavirus

Eva Girmanova,Irena Brabcova,Ondrej Viklicky,Mariana Wohlfartova,Jelena Skibova,Petra Hribova,Jiri Klema

doi:10.1155/2012/972102

Eva Girmanova, Irena Brabcova + Show 5 more

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https://doi.org/10.1155/2012/972102

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Abstract

BK polyomavirus infection is the important cause of virus-related nephropathy following kidney transplantation. BK virus reactivates in 30%–80% of kidney transplant recipients resulting in BK virus-related nephropathy in 1%–10% of cases. Currently, the molecular processes associated with asymptomatic infections in transplant patients infected with BK virus remain unclear. In this study we evaluate intrarenal molecular processes during different stages of BKV infection. The gene expression profiles of 90 target genes known to be associated with immune response were evaluated in kidney graft biopsy material using TaqMan low density array. Three patient groups were examined: control patients with no evidence of BK virus reactivation (n = 11), infected asymptomatic patients (n = 9), and patients with BK virus nephropathy (n = 10). Analysis of biopsies from asymptomatic viruria patients resulted in the identification of 5 differentially expressed genes (CD3E, CD68, CCR2, ICAM-1, and SKI) (P < 0.05), and functional analysis showed a significantly heightened presence of costimulatory signals (e.g., CD40/CD40L; P < 0.05). Gene ontology analysis revealed several biological networks associated with BKV immune control in comparison to the control group. This study demonstrated that asymptomatic BK viruria is associated with a different intrarenal regulation of several genes implicating in antiviral immune response.

Highlights

Innovations to immunosuppressive regimens have improved patient and kidney transplant survival rates; druginduced immune suppression has resulted in significant increases in complications associated with infections
BK polyomavirus (BKV) has been shown to reactivate in 30%–80% of kidney transplant recipients but only in 1%–10% of cases resulted in the development of BKV nephropathy (BKVN) associated with subsequent kidney graft deterioration and failure [2,3,4,5]
Cohorts of patients with asymptomatic viruria and the negative control group were established; we examined archived biopsies from patients with histologically proven BKV-associated nephropathy

Summary

Introduction

Innovations to immunosuppressive regimens have improved patient and kidney transplant survival rates; druginduced immune suppression has resulted in significant increases in complications associated with infections. BKV has been shown to reactivate in 30%–80% of kidney transplant recipients but only in 1%–10% of cases resulted in the development of BKV nephropathy (BKVN) associated with subsequent kidney graft deterioration and failure [2,3,4,5]. PCR screening has demonstrated that a majority of kidney transplant recipients are BKV positive in urine but not blood and never develop BKV nephropathy with graft function deterioration. It was shown that patients with asymptomatic viruria presented with significant BKV viral loads in kidney graft biopsy specimens [6], suggesting successful control of the BKV infection by the host immune system

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