Neutralization serotyping of BK polyomavirus infection in kidney transplant recipients.
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 ass...
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oai:doaj.org-article:35b03e41177a40098f4d2da80076af3c2021-11-18T06:04:31ZNeutralization serotyping of BK polyomavirus infection in kidney transplant recipients.1553-73661553-737410.1371/journal.ppat.1002650https://doaj.org/article/35b03e41177a40098f4d2da80076af3c2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22511874/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374BK 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.Diana V PastranaDaniel C BrennanNicolas CuburuGregory A StorchRaphael P ViscidiParmjeet S RandhawaChristopher B BuckPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 8, Iss 4, p e1002650 (2012) |
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Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 |
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Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Diana V Pastrana Daniel C Brennan Nicolas Cuburu Gregory A Storch Raphael P Viscidi Parmjeet S Randhawa Christopher B Buck Neutralization serotyping of BK polyomavirus infection in kidney transplant recipients. |
description |
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. |
format |
article |
author |
Diana V Pastrana Daniel C Brennan Nicolas Cuburu Gregory A Storch Raphael P Viscidi Parmjeet S Randhawa Christopher B Buck |
author_facet |
Diana V Pastrana Daniel C Brennan Nicolas Cuburu Gregory A Storch Raphael P Viscidi Parmjeet S Randhawa Christopher B Buck |
author_sort |
Diana V Pastrana |
title |
Neutralization serotyping of BK polyomavirus infection in kidney transplant recipients. |
title_short |
Neutralization serotyping of BK polyomavirus infection in kidney transplant recipients. |
title_full |
Neutralization serotyping of BK polyomavirus infection in kidney transplant recipients. |
title_fullStr |
Neutralization serotyping of BK polyomavirus infection in kidney transplant recipients. |
title_full_unstemmed |
Neutralization serotyping of BK polyomavirus infection in kidney transplant recipients. |
title_sort |
neutralization serotyping of bk polyomavirus infection in kidney transplant recipients. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2012 |
url |
https://doaj.org/article/35b03e41177a40098f4d2da80076af3c |
work_keys_str_mv |
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