A comparative study of Merkel cell, BK and JC polyomavirus infections in renal transplant recipients and healthy subjects

Husseiny, Mohamed I.; Anastasi, Bishoy; Singer, Jennifer S.; Lacey, Simon F.

doi:10.1016/j.jcv.2010.06.017

Cited by 69 publications

(71 citation statements)

References 24 publications

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“…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).…”

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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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confidence: 99%

BK Polyomavirus Genotypes Represent Distinct Serotypes with Distinct Entry Tropism

Pastrana

Ray

Magaldi

et al. 2013

J Virol

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“…BKPyV, JCPyV and TSPyV can be found in the kidney (Doerries, 2006;Fischer et al, 2012), whereas KIPyV, MCPyV, HPyV9 and STLPyV DNA can be detected in urine (Csoma et al, 2012(Csoma et al, , 2015Husseiny et al, 2010;Lim et al, 2013;Mertz et al, 2010;Rockett et al, 2013). The BKPyV, MCPyV and TSPyV early and late promoters were among the strongest in HEK293 cells.…”

Section: Discussionmentioning

confidence: 99%

Early and late promoters of BK polyomavirus, Merkel cell polyomavirus, Trichodysplasia spinulosa-associated polyomavirus and human polyomavirus 12 are among the strongest of all known human polyomaviruses in 10 different cell lines

Moens

Ghelue

Ludvigsen

et al. 2015

Journal of General Virology

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Early and late promoters of BK polyomavirus, Merkel cell polyomavirus, Trichodysplasia spinulosa-associated polyomavirus and human polyomavirus 12 are among the strongest of all known human polyomaviruses in 10 different cell lines Little is known about cell tropism of the novel HPyVs, and cell cultures allowing virus propagation are lacking. Because viral tropism partially depends on the interaction of cellular transcription factors with the viral promoter, we monitored the promoter activity of all known HPyVs. Therefore, we compared the relative early and late promoter activity of the BK polyomavirus (BKPyV) (WW strain) with the corresponding activities of the other HPyVs in 10 different cell lines derived from brain, colon, kidney, liver, lung, the oral cavity and skin. Our results show that the BKPyV, MCPyV, TSPyV and HPyV12 early promoters displayed the strongest activity in most cell lines tested, while the remaining HPyV had relative low early promoter activity. HPyV12 showed the highest late promoter activity of all HPyVs in most cell lines, but also the BKPyV, MCPyV and TSPyV late promoters belonged to the stronger ones among HPyVs. The HPyVs with weak early promoter activity had in general also weak late promoter activity, except for HPyV10 whose late promoter was relatively strong in six of the 10 cell lines. A 20 bp deletion in the promoter of an HPyV12 variant significantly affected both early and late promoter activity in most cell lines. In conclusion, our findings suggest which cell lines may be suitable for virus propagation and may give an indication of the cell tropism of the HPyVs.

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“…Despite the rarity of MCC, MCPyV is a common skin commensal, found in healthy individuals. It has also been detected in urine, in immunosuppressed organ transplant recipients and non-immunosuppressed subjects (Husseiny et al 2010;Signorini et al 2014).…”

Section: Discussionmentioning

confidence: 99%

First Detection of Human Papillomaviruses and Human Polyomaviruses in River Waters in Italy

et al. 2015

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Waterborne exposure to human viruses is possible through contact with contaminated water environments and can result in infections associated with a wide range of illnesses, including gastrointestinal, respiratory, ear, ocular, and skin infections. Recently, the occurrence in water environments of two groups of human viruses-both known with oncogenic potential, human polyomaviruses (HPyVs) and papillomaviruses (HPVs)-has been reported worldwide. These viruses, responsible for highly prevalent infections worldwide, have recently been proposed as potentially emerging waterborne pathogens. The objective of the present study was to examine the occurrence of HPyVs and HPVs in surface waters, by monitoring two rivers in Northwestern Italy, by nested PCR assays and sequencing. HPyVs (JC, BK, and Merkel cell polyomavirus) were detected in 10/25 (40%) samples. HPVs (HPV8, 17, 21, 25, 32, 80, 99, 105, and putative new HPVs) were identified in 14/25 (56%) river samples. The number of HPV DNA copies in waters was measured by quantitative real-time PCR. To our knowledge, this is the first detection and quantification of HPVs in surface waters. The possibility that HPyVs and HPVs can be transmitted by the waterborne route deserves to be explored in future studies.

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A comparative study of Merkel cell, BK and JC polyomavirus infections in renal transplant recipients and healthy subjects

Abstract: Background-Merkel cell carcinoma (MCC) is a rare skin cancer associated with immunosuppression and the integration of Merkel cell polyomavirus (MCPyV) DNA into the tumor cell genome. Little is known about the natural history of MCPyV infection.

Cited by 69 publications

References 24 publications

BK Polyomavirus Genotypes Represent Distinct Serotypes with Distinct Entry Tropism

BK Polyomavirus Genotypes Represent Distinct Serotypes with Distinct Entry Tropism

Early and late promoters of BK polyomavirus, Merkel cell polyomavirus, Trichodysplasia spinulosa-associated polyomavirus and human polyomavirus 12 are among the strongest of all known human polyomaviruses in 10 different cell lines

First Detection of Human Papillomaviruses and Human Polyomaviruses in River Waters in Italy

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