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Neutralization serotyping of BK polyomavirus infection in kidney transplant recipients

Pastrana, DV and Brennan, DC and Çuburu, N and Storch, GA and Viscidi, RP and Randhawa, PS and Buck, CB (2012) Neutralization serotyping of BK polyomavirus infection in kidney transplant recipients. PLoS Pathogens, 8 (4). ISSN 1553-7366

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Abstract

BK polyomavirus (BKV or BKPyV) associated nephropathy affects up to 10% of kidney transplant recipients (KTRs). BKV isolates are categorized into four genotypes. It is currently unclear whether the four genotypes are also serotypes. To address this issue, we developed high-throughput serological assays based on antibody-mediated neutralization of BKV genotype I and IV reporter vectors (pseudoviruses). Neutralization-based testing of sera from mice immunized with BKV-I or BKV-IV virus-like particles (VLPs) or sera from naturally infected human subjects revealed that BKV-I specific serum antibodies are poorly neutralizing against BKV-IV and vice versa. The fact that BKV-I and BKV-IV are distinct serotypes was less evident in traditional VLP-based ELISAs. BKV-I and BKV-IV neutralization assays were used to examine BKV type-specific neutralizing antibody responses in KTRs at various time points after transplantation. At study entry, sera from 5% and 49% of KTRs showed no detectable neutralizing activity for BKV-I or BKV-IV neutralization, respectively. By one year after transplantation, all KTRs were neutralization seropositive for BKV-I, and 43% of the initially BKV-IV seronegative subjects showed evidence of acute seroconversion for BKV-IV neutralization. The results suggest a model in which BKV-IV-specific seroconversion reflects a de novo BKV-IV infection in KTRs who initially lack protective antibody responses capable of neutralizing genotype IV BKVs. If this model is correct, it suggests that pre-vaccinating prospective KTRs with a multivalent VLP-based vaccine against all BKV serotypes, or administration of BKV-neutralizing antibodies, might offer protection against graft loss or dysfunction due to BKV associated nephropathy.

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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Pastrana, DV
Brennan, DC
Çuburu, N
Storch, GA
Viscidi, RP
Randhawa, PSpsr@pitt.eduPSR
Buck, CB
Contributors:
ContributionContributors NameEmailPitt UsernameORCID
EditorImperiale, MichaelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Date: 1 April 2012
Date Type: Publication
Journal or Publication Title: PLoS Pathogens
Volume: 8
Number: 4
DOI or Unique Handle: 10.1371/journal.ppat.1002650
Schools and Programs: School of Medicine > Pathology
Refereed: Yes
ISSN: 1553-7366
MeSH Headings: Animals; Antibodies, Neutralizing--blood; Antibodies, Neutralizing--immunology; Antibodies, Neutralizing--pharmacology; Antibodies, Viral; BK Virus--immunology; BK Virus--metabolism; Disease Models, Animal; Female; Humans; Kidney Diseases--immunology; Kidney Diseases--prevention & control; Kidney Transplantation; Male; Mice; Mice, Inbred BALB C; Polyomavirus Infections--blood; Polyomavirus Infections--immunology; Polyomavirus Infections--prevention & control; Time Factors; Vaccination--methods; Viral Vaccines--immunology; Viral Vaccines--pharmacology
Other ID: NLM PMC3325208
PubMed Central ID: PMC3325208
PubMed ID: 22511874
Date Deposited: 24 Sep 2012 20:26
Last Modified: 05 Feb 2019 01:55
URI: http://d-scholarship.pitt.edu/id/eprint/14172

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