Molecular Epidemiology of Merkel Cell Polyomavirus: Evidence for Geographically Related Variant Genotypes

Martel-Jantin, Claire; Filippone, Claudia; Tortevoye, Patricia; Afonso, Philippe V.; Betsem, Edouard; Descorps-Declère, Stéphane; Nicol, Jérôme; Touzé, Antoine; Coursaget, Pierre; Crouzat, M; Berthet, Nicolás; Cassar, Olivier; Gessain, Antoine

doi:10.1128/jcm.02348-13

Cited by 41 publications

(27 citation statements)

References 25 publications

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“…8-11 Infection often occurs in childhood and is typically self-limited. 11-13 However, among patients who develop MCC, MCPyV integrates into the human genome and undergoes tumor-specific truncating mutations and thus can no longer replicate (Fig 1B). 7, 14 Instead, viral oncoproteins (T-antigens) are persistently expressed in MCC tumors and help to promote cell cycle progression and tumorigenesis through multiple mechanisms, 15 including inhibition of the tumor-suppressor pRb, 16 stabilization of the oncoprotein c-Myc, 17 and evasion of innate immunity.…”

Section: Introductionmentioning

confidence: 99%

Viral oncoprotein antibodies as a marker for recurrence of Merkel cell carcinoma: A prospective validation study

Paulson

Lewis

Redman

et al. 2016

Cancer

149

127

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Background Merkel cell carcinoma (MCC) is an aggressive skin cancer with a recurrence rate of >40%. Of the 2000 MCC cases/year in the USA, most are caused by the Merkel cell polyomavirus (MCPyV). Antibodies to MCPyV-oncoprotein (T-antigens) have been correlated with MCC tumor burden. We prospectively validated the clinical utility of MCPyV oncoprotein antibody titers for MCC prognostication and surveillance. Methods MCPyV-oncoprotein antibody detection was optimized in a clinical laboratory. A cohort of 219 patients with newly-diagnosed MCC were followed prospectively (median follow-up 1.9 years). Among seropositive patients, antibody titer and disease status were serially tracked. Results Antibodies to MCPyV-oncoproteins were rare among healthy individuals (1%) but present in most MCC patients (114 of 219, 52%, p<0.01). Seropositivity at diagnosis independently predicted decreased recurrence risk (HR=0.58; p=0.04) in multivariate analyses adjusted for age, sex, stage, and immunosuppression. Following initial treatment, seropositive patients whose disease did not recur had rapidly falling titers that became negative by a median of 8.4 months. Among seropositive patients who underwent serial evaluation (71 patients; 282 timepoints), an increasing oncoprotein titer had a positive predictive value of 66% for clinically evident recurrence while a decreasing titer had a negative predictive value of 97%. Conclusions Determination of oncoprotein antibody titer assists in the clinical management of newly diagnosed MCC patients by stratifying them into a higher risk seronegative cohort in whom radiologic imaging may play a more prominent role, and into a lower-risk seropositive cohort whose disease status can be tracked in part via oncoprotein antibody titer.

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Section: Introductionmentioning

confidence: 99%

Viral oncoprotein antibodies as a marker for recurrence of Merkel cell carcinoma: A prospective validation study

Paulson

Lewis

Redman

et al. 2016

Cancer

149

127

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“…Recent studies have suggested the existence of geographically-related variants with five major MCPyV genotypes: Europe/North America, Africa (SubSaharan), Oceania, South America, and Asia/Japan, based on the analysis of a 1,284-bp long fragment of MCPyV (Martel-Jantin et al 2014). The complete identity of our sequence with sequences of all five groups suggests that the small T-antigen gene fragment amplified is highly conserved and may therefore not be useful for phylogenetic analysis.…”

Section: Discussionmentioning

confidence: 62%

Frequent and Abundant Merkel Cell Polyomavirus Detection in Urban Wastewaters in Italy

et al. 2014

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Viruses strongly associated with human cancer have recently been detected in urban sewages and other water environments worldwide. The aim of the present study was to assess the presence of Merkel cell polyomavirus (MCPyV), a newly discovered, potentially oncogenic human virus, in urban sewage samples collected at wastewater treatment plants (WTPs) in Italy. A total of 131 raw sewage samples were collected from 21 WTPs in nine Italian regions and analyzed by both qualitative (PCR/nested) and quantitative (Real-Time qRT-PCR) methods. Of these, 66 samples (50.3 %) were positive for MCPyV by the qualitative assay. Quantitative data showed high viral loads in wastewaters (mean, 1.5E + 05 genome copies/liter). High concentrations of MCPyV were found in all WTPs under study, suggesting a wide circulation of the virus and thus the need for further studies to assess possible waterborne MCPyV transmission.

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“…MCPYV belongs to the Orthopolyomavirus genus of the Polyomaviridae family, which include mammalian polyomaviruses such as murine PyV (MPyV), simian virus (SV40) and the human polyomaviruses JC (JCPyV) and BK (BKPyV) [1][2][3][4][5][6][7][8][9][10][11]. The genome is 5.4 kb which constitute two regions; the early region which encodes the large tumor (T) and small T antigens, and the late region which comprise the structural viral proteins VP1, VP2 and VP3, which form the viral capsid.…”

Section: Introductionmentioning

confidence: 99%

Prediction and Conservancy Analysis of Multiepitope Based Peptide Vaccine Against Merkel Cell Polyomavirus: An Immunoinformatics Approach

Awad-Elkareem¹,

Osman²,

Mohamed³

et al. 2017

Immunome Res

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Merkel cell Polyomavirus is non-enveloped, dsDNA virus belonging to Polyomaviridae family linked to an uncommon aggressive skin malignancy. The poor prognosis and limited understanding of disease pathogenesis warrants innovative treatment. In this current study we aim to predict TB cell immunogenic epitopes from the VP1 protein of all merkel cell polyomavirus strain which will aid in effective epitope based vaccine design using immuoinformatics approaches. We retrieved 423 full-length VP1 protein sequences of merkel cell polyomavirus species from the NCBI database. These sequences were analyzed to determine the conserved region and were used to predict the epitopes using the IEDB immunoinformatics algorithms. For B cell three epitope were predicted as peptide vaccine (QEKTVY, KTVYPK, and QEKTVYP). For T cell the predicted Class-I peptides (SLFSNLMPK, LQMWEAISV and LLVKGGVEV) were found to cover the maximum number of MHC I alleles. The highest scoring Class II MHC binding peptides were (IELYLNPRM, ISSLINVHY and INSLFSNLM). Further experiments will need to be undertaken to confirm the potential of these predicted epitopes in a future efficacious vaccine development.

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Molecular Epidemiology of Merkel Cell Polyomavirus: Evidence for Geographically Related Variant Genotypes

Cited by 41 publications

References 25 publications

Viral oncoprotein antibodies as a marker for recurrence of Merkel cell carcinoma: A prospective validation study

Viral oncoprotein antibodies as a marker for recurrence of Merkel cell carcinoma: A prospective validation study

Frequent and Abundant Merkel Cell Polyomavirus Detection in Urban Wastewaters in Italy

Prediction and Conservancy Analysis of Multiepitope Based Peptide Vaccine Against Merkel Cell Polyomavirus: An Immunoinformatics Approach

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