Neutralization Serotyping of BK Polyomavirus Infection in Kidney Transplant Recipients

PLoS Pathogens

Parmjeet S. Randhawa¹  Raphael P. Viscidi²  Nicolas Çuburu³  Diana V. Pastrana³  Christopher B. Buck³  Gregory A. Storch⁴  Daniel C. Brennan⁴ 

[1] Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, United States of America;Department of Pediatrics, Johns Hopkins Medical Center, Baltimore, Maryland, United States of America;Laboratory of Cellular Oncology, National Cancer Institute, Bethesda, Maryland, United States of America;Washington University School of Medicine, St. Louis, Missouri, United States of America

关键词: Antibodies;    Renal transplantation;    Enzyme-linked immunoassays;    Serology;    Antibody response;    Opportunistic infections;    Kidneys;    Vaccines;   

DOI  :  10.1371/journal.ppat.1002650

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY