Specific IgG Antibodies React to Mimotopes of BK Polyomavirus, a Small DNA Tumor Virus, in Healthy Adult Sera

Silvia Pietrobon,Francesca Lotito,Marco Manfrini,Ilaria Bononi,Andrea Puozzo,Fernanda Martini,Mauro G Tognon,Elisa Mazzoni,Pier Francesco Nocini,Giovanni Guerra,Federica Destro

doi:10.3389/fimmu.2017.00236

Silvia Pietrobon, Francesca Lotito + Show 9 more

Open Access

https://doi.org/10.3389/fimmu.2017.00236

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Abstract

BK polyomavirus (BKPyV) was isolated in 1971 from the urine of a kidney transplant patient. Soon after its identification, BKPyV was characterized as a kidney-tropic virus, which is responsible of a significant fraction of the rejection of transplant kidney in the host. Moreover, in experimental conditions, BKPyV is able to transform different types of animal and human cells and to induce tumors of different histotypes in experimental animals. BKPyV DNA sequences have been detected in healthy individuals and cancer patients using polymerase chain reaction/Shouthern blot hybridization methods. Serum antibodies against this polyomavirus were revealed using immunological techniques, which, however, cross-react with other polyomaviruses such as JC (JCPyV) and Simian Virus 40. These non-specific data indicate the need of novel immunological methods and new investigations to check in a specific manner, BKPyV spread in humans. To this aim, mimotopes from BKPyV structural capsid protein 1 (VP1) were employed for specific immunological reactions to IgG antibodies of human serum samples. An indirect enzyme-linked immunosorbent assay with synthetic peptides mimicking immunogenic epitopes of BKPyV VP1 was set up and employed to test sera of healthy adult subjects. Data from this innovative immunological assay indicate that serum antibodies against BKPyV VP1 mimotopes are detectable in healthy subjects ranging from 18 to 90 years old. The overall prevalence of serum samples that reacted to BKPyV VP1 mimotopes was 72%. The strong points from this investigation are the novelty of the immunological method, its simplicity of the approach, and the specificity of BKPyV antibody reaction to VP1 mimotopes.

Highlights

BK polyomavirus (BKPyV) was isolated in 1971 by Gardner et al from the urine of a renal transplant patient [1]
An indirect enzyme-linked immunosorbent assay (ELISA) was setup using synthetic peptides in order to check whether human sera contain IgG antibodies, which react to BKPyV peptides and to determine the spread of BKPyV infection in humans
Serum samples, which reacted to BKPyV viral capsid protein 1 (VP1)-L mimotope reached an overall prevalence of 80%

Summary

Introduction

BK polyomavirus (BKPyV) was isolated in 1971 by Gardner et al from the urine of a renal transplant patient [1]. BKPyV was characterized as a human polyomavirus (HPyV) with a circular double-stranded DNA of about 5.15 Kb [2]. BKPyV is able to transform human cells of different types and to induce tumors of different histotypes in experimental animals [3]. BKPyV primary infection occurs during childhood [2]. Some investigations shown that BKPyV could even be vertically transmitted from mother to embryo/fetus [4]. Many reports have indicated a high prevalence of serum IgG antibodies against BKPyV in different human populations worldwide [2, 5, 6], suggesting that BKPyV is a ubiquitous HPyV

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