Prevalence of BK virus subtype I in Germany

Krumbholz, Andi; Zell, Roland; Egerer, Renate; Sauerbrei, Andreas; Helming, Andrea; Gruhn, Bernd; Wutzler, Peter

doi:10.1002/jmv.20743

Cited by 52 publications

(54 citation statements)

References 52 publications

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“…Our findings raise the interesting question of whether different BKV genotypes or subgenotypes exhibit altered tissue tropism or different levels of virulence in vivo. Although previous studies have surveyed BKV genotypes found in nephropathic lesions (15,16,(37)(38)(39), these studies have relied on BKV-I-biased PCR primers that underestimate the abundance of BKV genotypes II, III, and IV (40). The possibility that commonly used PCR primers do not robustly detect non-genotype I BKVs (particularly in the case of individuals coinfected with multiple BKV genotypes) is consistent with our observation that BKV-II seroprevalence (Fig.…”

Section: Discussionsupporting

confidence: 89%

BK Polyomavirus Genotypes Represent Distinct Serotypes with Distinct Entry Tropism

Pastrana

Ray

Magaldi

et al. 2013

J Virol

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BK polyomavirus (BKV) causes significant urinary tract pathogenesis in immunosuppressed individuals, including kidney and bone marrow transplant recipients. It is currently unclear whether BKV-neutralizing antibodies can moderate or prevent BKV disease. We developed reporter pseudoviruses based on seven divergent BKV isolates and performed neutralization assays on sera from healthy human subjects. The results demonstrate that BKV genotypes I, II, III, and IV are fully distinct serotypes. While nearly all healthy subjects had BKV genotype I-neutralizing antibodies, a majority of subjects did not detectably neutralize genotype III or IV. Surprisingly, BKV subgenotypes Ib1 and Ib2 can behave as fully distinct serotypes. This difference is governed by as few as two residues adjacent to the cellular glycan receptor-binding site on the virion surface. Serological analysis of mice given virus-like particle (VLP)-based BKV vaccines confirmed these findings. Mice administered a multivalent VLP vaccine showed high-titer serum antibody responses that potently cross-neutralized all tested BKV genotypes. Interestingly, each of the neutralization serotypes bound a distinct spectrum of cell surface receptors, suggesting a possible connection between escape from recognition by neutralizing antibodies and cellular attachment mechanisms. The finding implies that different BKV genotypes have different cellular tropisms and pathogenic potentials in vivo. Individuals who are infected with one BKV serotype may remain humorally vulnerable to other BKV serotypes after implementation of T cell immunosuppression. Thus, prevaccinating organ transplant recipients with a multivalent BKV VLP vaccine might reduce the risk of developing posttransplant BKV disease. BK polyomaviruses (BKVs or BKPyVs) are a species of icosahedral, nonenveloped, double-stranded DNA viruses. The genomes of all known full-length isolates of BKV can be categorized into four discrete genotypes based on analyses of nucleotide sequences (1). The prevalence and sequence characteristics of each genotype are thought to vary within different human populations worldwide (2).Studies indicate that 83 to 98% of individuals show serum antibody responses to the BKV genotype I (BKV-I) major capsid protein, VP1, by the time they are 21 years of age (3). The virus is thought to establish a lifelong chronic infection in the urinary epithelium, and virions are periodically shed at low levels in the urine of 5 to 27% of healthy adults (4, 5). Although BKV-I can cause malignancy in animal model systems, conclusive evidence showing a causal connection between BKVs and human cancer is still lacking (reviewed in reference 6). While it remains uncertain whether BKVs cause pathology in healthy individuals, it is clear that certain T cell-immunosuppressed individuals, such as recipients of kidney or bone marrow transplants, are at risk of developing uncontrolled BKV replication that leads to nephropathy or hemorrhagic cystitis, respectively (reviewed in reference 7). Currently available antiv...

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Section: Discussionsupporting

confidence: 89%

BK Polyomavirus Genotypes Represent Distinct Serotypes with Distinct Entry Tropism

Pastrana

Ray

Magaldi

et al. 2013

J Virol

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“…BKV strains of subtype I (66.64%) and subtype IV were detected in our samples. This result corresponds to the distribution of BKV subtypes in Europe analyzed in previous studies [Ikegaya et al, 2006;Krumbholz et al, 2006]. Subgroup Ib-2 BKV isolates are the most prevalent BKV strains in our German cohort (60.00%).…”

Section: Discussionsupporting

confidence: 90%

Mutations in the BC‐loop of the BKV VP1 region do not influence viral load in renal transplant patients

Krautkrämer

Klein

Sommerer

et al. 2008

Journal of Medical Virology

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The reactivation and replication of the BK polyomavirus (BKV) leading to BKV-associated nephropathy (BKVAN) is one of the major complications in renal transplantation patients. BKV isolates were classified into four subtypes (I-IV) based on genotype variations within the VP1-coding region. The type-specific amino acid differences cluster within the BC-loop of the major capsid protein VP1. As demonstrated in vitro, mutations in this region also play a role in the infectivity, attachment and stability of viral particles. Therefore, we analyzed the prevalence of BC-loop mutations in isolates of kidney transplant patients and compared their viral load in the urine. The VP1 subtyping regions of BKV isolates obtained from urine samples of 45 renal transplant patients were sequenced. The phylogenetic analysis of these sequences revealed that subtype I (66.67%) is the most prevalent genotype. The remaining isolates belong to subtype IV (33.33%). A high frequency of changes to specific amino acids within the BC-loop was identified among the BKV isolates from renal transplant patients. Patients with BKVAN exhibited a higher viral replication than patients without nephropathy. Although titers of isolates of subtype I were higher than titers of subtype IV isolates, the difference did not reach statistical significance. In addition, amino acid changes in the BC-loop did not influence the viral load and the incidence of BKVAN. These in vivo results demonstrate that high replication rates which serve as a predictive marker for BKVAN are not caused by altered receptor binding or affinity via mutated BC-loops.

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“…The distribution of BKV subtypes and subgroups in human populations has been studied in many countries (7)(8)(9). BKV subtype I subgroup distributions vary across countries; subgroup Ia is highly prevalent in Africa, subgroup Ib-1 is highly prevalent in southeast Asia, subgroup Ib-2 is highly prevalent in Europe, and subgroup Ic is highly prevalent in northeast Asia (10,11). As with subtype I, each subtype IV subgroup has a specific geographic distribution (6).…”

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confidence: 99%

A Simple and Reliable Strategy for BK Virus Subtyping and Subgrouping

et al. 2017

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BK virus (BKV)-associated diseases in transplant recipients are an emerging issue. However, identification of the various BK virus subtypes/subgroups is a long and delicate process on the basis of currently available data. Therefore, we wanted to define a simple and effective one-step strategy for characterizing all BK virus strains from the VP1 gene sequence. Based on the analysis of 199 available complete DNA VP1 sequences, phylogenetic trees, alignments, and isolated polymorphisms were used to define an effective strategy for distinguishing the 12 different BK virus subtypes/subgroups. Based on the 12 subtypes identified from the 199 complete BKV VP1 sequences (1,089 bp), 60 mutations that can be used to differentiate these various subtypes/subgroups were identified. Some genomic areas were more variable and comprised mutational hot spots. From a subregion of only 100 bp in the VP1 region (1977 through 2076), we therefore constructed an algorithm that enabled rapid determination of all BKV subtypes/subgroups with 99% agreement (197/199) relative to the complete VP1 sequence. We called this domain of the BK viral genome the BK typing and grouping region (BKTGR). Finally, we validated our viral subtype identification process in a population of 100 transplant recipients with 100% efficiency. The new simpler method of BKV subtyping/subgrouping reported here constitutes a useful tool for future studies that will help us to more clearly understand the impact of BKV subtypes/subgroups on diagnosis, infection, and BK virus-associated diseases.

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Prevalence of BK virus subtype I in Germany

Cited by 52 publications

References 52 publications

BK Polyomavirus Genotypes Represent Distinct Serotypes with Distinct Entry Tropism

BK Polyomavirus Genotypes Represent Distinct Serotypes with Distinct Entry Tropism

Mutations in the BC‐loop of the BKV VP1 region do not influence viral load in renal transplant patients

A Simple and Reliable Strategy for BK Virus Subtyping and Subgrouping

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