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J Virol. 2010 Jul;84(14):7064-72. doi: 10.1128/JVI.02400-09. Epub 2010 May 5.

Merkel cell polyomavirus-infected Merkel cell carcinoma cells require expression of viral T antigens.

Author information

1
Molecular Virology Program, University of Pittsburgh Cancer Institute, 5117 Centre Ave., Pittsburgh, PA 15213, USA.

Abstract

Merkel cell carcinoma (MCC) is the most aggressive skin cancer. Recently, it was demonstrated that human Merkel cell polyomavirus (MCV) is clonally integrated in approximately 80% of MCC tumors. However, direct evidence for whether oncogenic viral proteins are needed for the maintenance of MCC cells is still missing. To address this question, we knocked down MCV T-antigen (TA) expression in MCV-positive MCC cell lines using three different short hairpin RNA (shRNA)-expressing vectors targeting exon 1 of the TAs. The MCC cell lines used include three newly generated MCV-infected cell lines and one MCV-negative cell line from MCC tumors. Notably, all MCV-positive MCC cell lines underwent growth arrest and/or cell death upon TA knockdown, whereas the proliferation of MCV-negative cell lines remained unaffected. Despite an increase in the number of annexin V-positive, 7-amino-actinomycin D (7-AAD)-negative cells upon TA knockdown, activation of caspases or changes in the expression and phosphorylation of Bcl-2 family members were not consistently detected after TA suppression. Our study provides the first direct experimental evidence that TA expression is necessary for the maintenance of MCV-positive MCC and that MCV is the infectious cause of MCV-positive MCC.

PMID:
20444890
PMCID:
PMC2898224
DOI:
10.1128/JVI.02400-09
[Indexed for MEDLINE]
Free PMC Article

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