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:	Diana V Pastrana, Yanis L Tolstov, Jürgen C Becker, Patrick S Moore, Yuan Chang, Christopher B Buck
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2009
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/ed85563605c0437bb30bca5c25c5b3c9
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spelling	oai:doaj.org-article:ed85563605c0437bb30bca5c25c5b3c92021-11-25T05:47:39ZQuantitation of human seroresponsiveness to Merkel cell polyomavirus.1553-73661553-737410.1371/journal.ppat.1000578https://doaj.org/article/ed85563605c0437bb30bca5c25c5b3c92009-09-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/19750217/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Merkel 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.Diana V PastranaYanis L TolstovJürgen C BeckerPatrick S MooreYuan ChangChristopher B BuckPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 5, Iss 9, p e1000578 (2009)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Diana V Pastrana Yanis L Tolstov Jürgen C Becker Patrick S Moore Yuan Chang Christopher B Buck Quantitation of human seroresponsiveness to Merkel cell polyomavirus.
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.
format	article
author	Diana V Pastrana Yanis L Tolstov Jürgen C Becker Patrick S Moore Yuan Chang Christopher B Buck
author_facet	Diana V Pastrana Yanis L Tolstov Jürgen C Becker Patrick S Moore Yuan Chang Christopher B Buck
author_sort	Diana V Pastrana
title	Quantitation of human seroresponsiveness to Merkel cell polyomavirus.
title_short	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_sort	quantitation of human seroresponsiveness to merkel cell polyomavirus.
publisher	Public Library of Science (PLoS)
publishDate	2009
url	https://doaj.org/article/ed85563605c0437bb30bca5c25c5b3c9
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Quantitation of human seroresponsiveness to Merkel cell polyomavirus.

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