Human Merkel cell polyomavirus infection I. MCV T antigen expression in Merkel cell carcinoma, lymphoid tissues and lymphoid tumors

Masahiro Shuda, Reety Arora, H. J. Kwun, Huichen Feng, Ronit Sarid, María Teresa Fernández-Figueras, Yanis Tolstov, Ole Gjoerup, Mahesh M. Mansukhani, Steven H. Swerdlow, Preet M. Chaudhary, John M. Kirkwood, Michael A. Nalesnik, Jeffrey A. Kant, Lawrence M. Weiss, Patrick S. Moore, Yuan Chang

Research output: Contribution to journalArticlepeer-review

276 Scopus citations

Abstract

Merkel cell polyomavirus (MCV) is a recently discovered human virus closely related to African green monkey lymphotropic polyomavirus. MCV DNA is integrated in ̃80% of Merkel cell carcinomas (MCC), a neuroendocrine skin cancer linked to lymphoid malignancies such as chronic lymphocytic leukemia (CLL). To assess MCV infection and its association with human diseases, we developed a monoclonal antibody that specifically recognizes endogenous and transfected MCV large T (LT) antigen. We show expression of MCV LT protein localized to nuclei of tumor cells from MCC having PCR quantified MCV genome at an average of 5.2 (range 0.8-14.3) T antigen DNA copies per cell. Expression of this putative viral oncoprotein in tumor cells provides the mechanistic underpinning supporting the notion that MCV causes a subset of MCC. In contrast, although 2.2% of 325 hematolymphoid malignancies surveyed also showed evidence for MCV infection by DNA PCR, none were positive at high viral copy numbers, and none of 173 lymphoid malignancies examined on tissue microarrays expressed MCV LT protein in tumor cells. As with some of the other human polyomaviruses, lymphocytes may serve as a tissue reservoir for MCV infection, but hematolymphoid malignancies associated with MCC are unlikely to be caused by MCV.

Original languageEnglish (US)
Pages (from-to)1243-1249
Number of pages7
JournalInternational Journal of Cancer
Volume125
Issue number6
DOIs
StatePublished - Sep 15 2009

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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