Serological typing scheme for bk‐like isolates of human polyomavirus

Knowles, Wendy A.; Gibson, Peter H.; Gardner, S. D.

doi:10.1002/jmv.1890280212

Cited by 67 publications

(38 citation statements)

References 15 publications

(7 reference statements)

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“…Based on VP1 sequence data and restriction enzyme analysis, Jin et al (20) designed a typing scheme whereby all the existing BKV isolates are classified into four genotypes, which have been designated types I, II, III, and IV. These genotypes correlated well with the serotypes defined by Knowles et al (24). Knowledge of genetic variation in other regions of the viral genome is limited, even though a number of other functionally important proteins are coded by the virus.…”

supporting

confidence: 77%

Phylogenetic Analysis of Polyomavirus BK Sequences

Sharma

Gupta

Vats

et al. 2006

J Virol

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Polyomavirus BK (BKV) has emerged as an important pathogen in kidney transplant patients. Existing taxonomic classifications of BKV come from conventional DNA sequence alignments based on limited data derived from the VP1 gene. We have used a phylogenetic whole-genome approach to examine the pattern of diversity and evolutionary relationships between 45 BKV strains isolated from multiple clinical settings. This analysis supports the classification of BKV into six genotypes, of which types V and VI have not been previously recognized. BKV strains hitherto classified as type I are, in fact, quite heterogeneous, and several cluster with our newly defined genotypes V and VI. The sequence information needed for assigning genotypes can be captured by VP1, VP2, VP3, or large T-gene sequencing. The most polymorphic coding region in the viral genome is VP1, but significant variation is also present in the large T-antigen gene, wherein polymorphisms are found in 11.39% of all nucleotide sites, 46.22% of which are cluster specific. Type-specific amino acid changes within the VP1 region are predicted to map to the BC and DE loops. The number of taxonomically informative amino acid changes in the large T antigen exceeds even that of the VP1 region. Viral strains isolated from healthy subjects and from patients with human immunodeficiency virus infection, WiskottAldrich syndrome, and vasculopathy with capillary leak syndrome formed distinct subclusters. However, within the kidney transplant population, BKV strains derived from patients with asymptomatic viruria did not show complete separation from strains associated with allograft nephropathy.Polyomavirus BK (BKV) has a worldwide seroprevalence of 60 to 80% in humans (10). Primary infection occurs in childhood (11) and leads to viral latency in the urogenital tract and mononuclear cells. Following reactivation, which mostly occurs in immunocompromised patients, the virus is excreted in the urine (5). BKV viruria in renal transplant recipients ranges between 10 to 60% and has been associated with ureteric stenosis (16) and BK viral nephropathy characterized by tubular necrosis and interstitial nephritis (32, 33). In bone marrow transplant recipients, BKV has been linked to hemorrhagic cystitis (13,26,34).Characterization of genetic diversity of BK virus has biologic as well as clinical implications. This information is needed to seek potential relationships between viral genotype and clinical disease. Sequence data are required by diagnostic virology laboratories to ensure that primers and probes being used for amplification of viral DNA can successfully detect all naturally occurring viral strains. One of the most variable regions of the viral genome is the noncoding control region (NCCR), which shows insertions, deletions, duplications, and complex rearrangements involving enhancer and/or promoter sequences (28, 29). Significant variation is also recognized in the VP1 gene, which codes for VP1, a major structural protein that comprises approximately 80% of the total viral c...

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supporting

confidence: 77%

Phylogenetic Analysis of Polyomavirus BK Sequences

Sharma

Gupta

Vats

et al. 2006

J Virol

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“…For rotaviruses, a 20-fold difference in neutralizing titer between cognate and noncognate types is sufficient to apply the distinction (22), while for adenovirus, 8-to 16-fold differences define serotypes (23). For BKV, a very wide range of titers has been used to define serotypes (4-to 100-fold difference) (9,24). For this study, we chose a conservative definition of at least a 100-fold difference in neutralizing titer between two BKV variants for at least one human serum sample.…”

Section: Resultsmentioning

confidence: 99%

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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“…MCV serology has been studied mainly in American and European populations using only two different MCV VP1 sequences. Additional studies are needed to investigate the existence of variations within the VP1 sequence on different continents and whether the VLPs derived from the different strains have different reactivity with sera of different geographical origins, as was previously shown for human papillomaviruses (13,19), and also to investigate the possibility of the existence of serotypes as observed for BKV (11).…”

Section: Discussionmentioning

confidence: 96%

Generation of Merkel Cell Polyomavirus (MCV)-Like Particles and Their Application to Detection of MCV Antibodies

et al. 2010

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The genome of a new human polyomavirus, known as Merkel cell polyomavirus (MCV), has recently been reported to be integrated within the cellular DNA of Merkel cell carcinoma (MCC), a rare human skin cancer. To investigate MCV seroprevalence in the general population, we expressed three different MCV VP1 in insect cells using recombinant baculoviruses. Viruslike particles (VLPs) were obtained with only one of the three VP1 genes. High-titer antibodies against VP1 VLPs were detected in mice immunized with MCV VLPs, and limited crossreactivity was observed with BK polyomavirus (BKV) and lymphotropic polyomavirus (LPV). MCV antibodies were detected in 77% of the general population, with no variations according to age.Polyomaviruses are small, nonenveloped DNA viruses, with a double-stranded circular DNA genome of ϳ5 kbp packaged within a capsid about 45 nm in diameter. The polyomavirus capsid is composed of three structural proteins: VP1, the major capsid protein, and VP2 and VP3, the minor capsid proteins. Twenty members of the polyomavirus family have been identified to date (24) and, with the exception of the murine pneumotropic polyomavirus and the avian polyomavirus, primary infection is generally asymptomatic. Five polyomaviruses infect humans, including the ubiquitous BK polyomavirus (BKV) and JC polyomavirus (JCV), which cause persistent and/or latent infections and the recently identified KI and WU polyomaviruses isolated from pulmonary secretions (1, 6). A new polyomavirus, the Merkel cell polyomavirus (MCV), was recently discovered in human Merkel cell carcinomas (MCC) (4). MCC is a relatively rare skin cancer in elderly or immunosuppressed patients and is one of the most lethal skin cancers (8). The annual incidence rate of this aggressive primary cutaneous neuroendocrine carcinoma in the United States was reported to be 0.44 per 100,000 inhabitants in 2001 and tripled between 1986 and 2001 (8), and this trend is continuing (7). An incidence of 0.13 cases per 100,000 was recently reported in France (15). Clonal integration of the MCV genome within the tumor genome (4) and the deletions and/or mutations observed within the T antigen gene (17) have suggested a direct oncogenic role for MCV. However, the prevalence and pathogenicity of this newly discovered MCV have yet to be fully investigated.The aim of the study was to produce MCV viruslike particles (VLPs) and to investigate the presence of MCV antibodies in the general population of Europe. MCV VLPs were obtained with only one of the three MCV VP1 strains investigated, and these VLPs were used to investigate cross-reactivity against other polyomaviruses and for the determination of the prevalence of MCV antibodies in the general European population. MATERIALS AND METHODSGeneration of VLPs for MCV, BKV, and LPV polyomaviruses. Expression of the VP1 protein was performed using the MCC350 VP1 prototype sequence and the VP1 sequences amplified from two French MCC patients (MKT-21 and MKT-26) (EMBL FM864207 and FM864209, respectively) (21). MCC350 VP1 codi...

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Serological typing scheme for bk‐like isolates of human polyomavirus

Cited by 67 publications

References 15 publications

Phylogenetic Analysis of Polyomavirus BK Sequences

Phylogenetic Analysis of Polyomavirus BK Sequences

BK Polyomavirus Genotypes Represent Distinct Serotypes with Distinct Entry Tropism

Generation of Merkel Cell Polyomavirus (MCV)-Like Particles and Their Application to Detection of MCV Antibodies

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