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Quantitation of Human Seroresponsiveness to Merkel Cell Polyomavirus

Merkel cell carcinoma (MCC) is a relatively uncommon but highly lethal form of skin cancer. A majority of MCC tumors carry DNA sequences derived from a newly identified virus called Merkel cell polyomavirus (MCV or MCPyV), a candidate etiologic agent underlying the development of MCC. To further inv...

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Autores principales: Pastrana, Diana V., Tolstov, Yanis L., Becker, Jürgen C., Moore, Patrick S., Chang, Yuan, Buck, Christopher B.
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2734180/
https://www.ncbi.nlm.nih.gov/pubmed/19750217
http://dx.doi.org/10.1371/journal.ppat.1000578
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author Pastrana, Diana V.
Tolstov, Yanis L.
Becker, Jürgen C.
Moore, Patrick S.
Chang, Yuan
Buck, Christopher B.
author_facet Pastrana, Diana V.
Tolstov, Yanis L.
Becker, Jürgen C.
Moore, Patrick S.
Chang, Yuan
Buck, Christopher B.
author_sort Pastrana, Diana V.
collection PubMed
description Merkel cell carcinoma (MCC) is a relatively uncommon but highly lethal form of skin cancer. A majority of MCC tumors carry DNA sequences derived from a newly identified virus called Merkel cell polyomavirus (MCV or MCPyV), a candidate etiologic agent underlying the development of MCC. To further investigate the role of MCV infection in the development of MCC, we developed a reporter vector-based neutralization assay to quantitate MCV-specific serum antibody responses in human subjects. Our results showed that 21 MCC patients whose tumors harbored MCV DNA all displayed vigorous MCV-specific antibody responses. Although 88% (42/48) of adult subjects without MCC were MCV seropositive, the geometric mean titer of the control group was 59-fold lower than the MCC patient group (p<0.0001). Only 4% (2/48) of control subjects displayed neutralizing titers greater than the mean titer of the MCV-positive MCC patient population. MCC tumors were found not to express detectable amounts of MCV VP1 capsid protein, suggesting that the strong humoral responses observed in MCC patients were primed by an unusually immunogenic MCV infection, and not by viral antigen expressed by the MCC tumor itself. The occurrence of highly immunogenic MCV infection in MCC patients is unlikely to reflect a failure to control polyomavirus infections in general, as seroreactivity to BK polyomavirus was similar among MCC patients and control subjects. The results support the concept that MCV infection is a causative factor in the development of most cases of MCC. Although MCC tumorigenesis can evidently proceed in the face of effective MCV-specific antibody responses, a small pilot animal immunization study revealed that a candidate vaccine based on MCV virus-like particles (VLPs) elicits antibody responses that robustly neutralize MCV reporter vectors in vitro. This suggests that a VLP-based vaccine could be effective for preventing the initial establishment of MCV infection.
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spelling pubmed-27341802009-09-11 Quantitation of Human Seroresponsiveness to Merkel Cell Polyomavirus Pastrana, Diana V. Tolstov, Yanis L. Becker, Jürgen C. Moore, Patrick S. Chang, Yuan Buck, Christopher B. PLoS Pathog Research Article Merkel cell carcinoma (MCC) is a relatively uncommon but highly lethal form of skin cancer. A majority of MCC tumors carry DNA sequences derived from a newly identified virus called Merkel cell polyomavirus (MCV or MCPyV), a candidate etiologic agent underlying the development of MCC. To further investigate the role of MCV infection in the development of MCC, we developed a reporter vector-based neutralization assay to quantitate MCV-specific serum antibody responses in human subjects. Our results showed that 21 MCC patients whose tumors harbored MCV DNA all displayed vigorous MCV-specific antibody responses. Although 88% (42/48) of adult subjects without MCC were MCV seropositive, the geometric mean titer of the control group was 59-fold lower than the MCC patient group (p<0.0001). Only 4% (2/48) of control subjects displayed neutralizing titers greater than the mean titer of the MCV-positive MCC patient population. MCC tumors were found not to express detectable amounts of MCV VP1 capsid protein, suggesting that the strong humoral responses observed in MCC patients were primed by an unusually immunogenic MCV infection, and not by viral antigen expressed by the MCC tumor itself. The occurrence of highly immunogenic MCV infection in MCC patients is unlikely to reflect a failure to control polyomavirus infections in general, as seroreactivity to BK polyomavirus was similar among MCC patients and control subjects. The results support the concept that MCV infection is a causative factor in the development of most cases of MCC. Although MCC tumorigenesis can evidently proceed in the face of effective MCV-specific antibody responses, a small pilot animal immunization study revealed that a candidate vaccine based on MCV virus-like particles (VLPs) elicits antibody responses that robustly neutralize MCV reporter vectors in vitro. This suggests that a VLP-based vaccine could be effective for preventing the initial establishment of MCV infection. Public Library of Science 2009-09-11 /pmc/articles/PMC2734180/ /pubmed/19750217 http://dx.doi.org/10.1371/journal.ppat.1000578 Text en This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. https://creativecommons.org/publicdomain/zero/1.0/ This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration, which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose.
spellingShingle Research Article
Pastrana, Diana V.
Tolstov, Yanis L.
Becker, Jürgen C.
Moore, Patrick S.
Chang, Yuan
Buck, Christopher B.
Quantitation of Human Seroresponsiveness to Merkel Cell Polyomavirus
title Quantitation of Human Seroresponsiveness to Merkel Cell Polyomavirus
title_full Quantitation of Human Seroresponsiveness to Merkel Cell Polyomavirus
title_fullStr Quantitation of Human Seroresponsiveness to Merkel Cell Polyomavirus
title_full_unstemmed Quantitation of Human Seroresponsiveness to Merkel Cell Polyomavirus
title_short Quantitation of Human Seroresponsiveness to Merkel Cell Polyomavirus
title_sort quantitation of human seroresponsiveness to merkel cell polyomavirus
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2734180/
https://www.ncbi.nlm.nih.gov/pubmed/19750217
http://dx.doi.org/10.1371/journal.ppat.1000578
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