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.
Highlights
The process of kidney transplantation has been revolutionized since the first successful case in identical twins more than 5 decades ago [1,2]
Serological studies have shown that most humans are chronically infected with BK polyomavirus (BKV)
Using a novel neutralization-based approach, we found that about half of 108 kidney transplant recipients (KTRs) did not have detectable levels of antibodies capable of neutralizing BKV genotype IV (BKV-IV) at the time of transplantation
Summary
The process of kidney transplantation has been revolutionized since the first successful case in identical twins more than 5 decades ago [1,2]. The use of immunosuppressants such as cyclosporine has made renal allografts a viable clinical option [3], but the process still has many challenges, including the management of chronic and acute immune-mediated rejection of the allograft, nephrotoxicity from immunosuppressants and antiviral drugs, and controlling opportunistic infections. BKV can cause a bladder condition known as hemorrhagic cystitis in bone marrow transplant recipients and in cancer patients treated with the immunosuppressant cyclophosphamide [12,13] Clinical guidelines for these conditions recommend regular monitoring of serum or urinary BKV viral load and reduction of immunosuppression if signs of uncontrolled BKV replication are observed [4]
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have