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Molecular networks involved in the immune control of BK polyomavirus.

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.

SUBMITTER: Girmanova E

PROVIDER: S-EPMC3521483 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Molecular networks involved in the immune control of BK polyomavirus.

Girmanova Eva E Brabcova Irena I Klema Jiri J Hribova Petra P Wohlfartova Mariana M Skibova Jelena J Viklicky Ondrej O

Clinical & developmental immunology 20121205

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 profil ...[more]

PMID: 23251224

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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.

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Molecular networks involved in the immune control of BK polyomavirus.

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Molecular networks involved in the immune control of BK polyomavirus.

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