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Quantitation of human seroresponsiveness to Merkel cell polyomavirus

Pastrana, DV and Tolstov, YL and Becker, JC and Moore, PS and Chang, Y and Buck, CB (2009) Quantitation of human seroresponsiveness to Merkel cell polyomavirus. PLoS Pathogens, 5 (9). ISSN 1553-7366

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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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Item Type: Article
Status: Published
CreatorsEmailPitt UsernameORCID
Pastrana, DV
Tolstov, YL
Becker, JC
Moore, PSpsm9@pitt.eduPSM9
Chang, Yyc70@pitt.eduYC70
Buck, CB
ContributionContributors NameEmailPitt UsernameORCID
Centers: Other Centers, Institutes, Offices, or Units > Pittsburgh Cancer Institute
Date: 1 September 2009
Date Type: Publication
Journal or Publication Title: PLoS Pathogens
Volume: 5
Number: 9
DOI or Unique Handle: 10.1371/journal.ppat.1000578
Refereed: Yes
ISSN: 1553-7366
MeSH Headings: Animals; Antibodies, Viral--blood; Antibodies, Viral--metabolism; Capsid Proteins--genetics; Capsid Proteins--immunology; Capsid Proteins--metabolism; Carcinoma, Merkel Cell--immunology; Carcinoma, Merkel Cell--virology; Cell Line; Genes, Reporter--genetics; Genes, Reporter--immunology; Humans; Immunoenzyme Techniques; Immunohistochemistry; Male; Mice; Neutralization Tests--methods; Polyomavirus--immunology; Polyomavirus--pathogenicity; Rabbits
Other ID: NLM PMC2734180
PubMed Central ID: PMC2734180
PubMed ID: 19750217
Date Deposited: 03 Aug 2012 16:14
Last Modified: 01 Feb 2019 15:57


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