Development and evaluation of a BK polyomavirus serotyping assay using Luminex technology

• Published in: Journal of clinical virology Vol. 110; pp. 22 - 28
• Main Authors: Wunderink, Herman F., de Brouwer, Caroline S., van der Meijden, Els, Pastrana, Diana V., Kroes, Aloysius C.M., Buck, Christopher B., Feltkamp, Mariet C.W.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.01.2019
• Subjects: Antibodies, Viral - blood; BK polyomavirus; BK Virus - classification; Cross Reactions; Genotype; Genotypes; Humans; Immunoassay - methods; Immunoglobulin G - blood; Kidney Transplantation; Polyomavirus Infections - virology; Serogroup; Serotypes; Serotyping - methods; Transplant Recipients; Tumor Virus Infections - virology; Serotypes; Genotypes; BK polyomavirus; Kidney transplantation
• ISSN: 1386-6532; 1873-5967
• DOI: 10.1016/j.jcv.2018.11.009

•Seroreactivity against BKPyV is common and directed against multiple genotypes.•The most prevalent and strongest seroresponses are directed against BKPyV genotype I.•Crossreactivity is seen among genotype I subtypes and among genotypes II, III and IV.•Genotype I and IV represent individual serotypes.•Strong BKPyV genotype-specific responses exhibit virus neutralizing activity. The BK polyomavirus (BKPyV) is subdivided into four genotypes. The consequences of each genotype and of donor-recipient genotype (mis)match for BKPyV-associated nephropathy (BKPyVAN) in kidney transplant recipients (KTRs) are unknown. To develop and evaluate a genotype-specific IgG antibody-based BKPyV serotyping assay, in order to classify kidney transplant donors and recipients accordingly. VP1 antigens of six BKPyV variants (Ib1, Ib2, Ic, II, III and IV) were expressed as recombinant glutathione-s-transferase-fusion proteins and coupled to fluorescent Luminex beads. Sera from 87 healthy blood donors and 39 KTRs were used to analyze seroreactivity and serospecificity against the different BKPyV genotypes. Six sera with marked BKPyV serotype profiles were analyzed further for genotype-specific BKPyV pseudovirus neutralizing capacity. Seroreactivity was observed against all genotypes, with seropositivity rates above 77% comparable for KTRs and blood donors. Strong cross-reactivity (r > 0.8) was observed among genotype I subtypes, and among genotypes II, III and IV. Seroresponses against genotypes I and IV seemed genuine, while those against II and III could be out(cross)competed. GMT (Luminex) and IC50 (neutralization assay) values showed good agreement in determining the genotype with the strongest seroresponse within an individual. Despite some degree of cross-reactivity, this serotyping assay seems a useful tool to identify the main infecting BKPyV genotype within a given individual. This information, which cannot be obtained otherwise from nonviremic/nonviruric individuals, could provide valuable information regarding the prevalent BKPyV genotype in kidney donors and recipients and warrants further study.