Merkel Cell Polyomavirus: A Causal Factor in Merkel Cell Carcinoma

Ghelue, Marijke Van; Moens, Ugo

doi:10.5772/25675

Cited by 1 publication

(2 citation statements)

References 161 publications

(220 reference statements)

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“…The original study showed that 8 out of the 10 examined MCC samples contained MCPyV DNA [1]. Numerous studies by different groups worldwide have confirmed that approximately 80% of MCCs are positive for this virus [2][3][4][5]. Because cell culture and transgenic mice studies have shown that MCPyV has an oncogenic potential that can be attributed to its viral proteins large T-antigen (LT) and small t-antigen (sT) ( [6][7][8][9]), and the association of the virus with MCC, MCPyV is considered an etiological factor in MCC and is classified as probably carcinogenic to humans [10].…”

Section: Introductionmentioning

confidence: 99%

“…Because cell culture and transgenic mice studies have shown that MCPyV has an oncogenic potential that can be attributed to its viral proteins large T-antigen (LT) and small t-antigen (sT) ( [6][7][8][9]), and the association of the virus with MCC, MCPyV is considered an etiological factor in MCC and is classified as probably carcinogenic to humans [10]. Two hallmarks of MCPyV-positive MCCs are the integration of the viral genome in the host chromosome and expression of a truncated version of LT [5,11]. Integration disrupts the late region so that no infectious particles are generated in MCCs, while the truncation of LT results in a non-DNA binding variant that retains the ability to bind the tumor suppressor retinoblastoma protein, but not p53 [12].…”

Section: Introductionmentioning

confidence: 99%

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Promoter activity of Merkel cell Polyomavirus variants in human dermal fibroblasts and a Merkel cell carcinoma cell line

Abdulsalam

Rasheed

Sveinbjørnsson

et al. 2020

Virol J

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Background: Merkel cell polyomavirus (MCPyV) is a human polyomavirus that establishes a lifelong harmless infection in most individuals, with dermal fibroblasts believed to be the natural host cell. However, this virus is the major cause of Merkel cell carcinoma (MCC), an aggressive skin cancer. Several MCPyV variants with polymorphism in their promoter region have been isolated, but it is not known whether these differences affect the biological properties of the virus. Methods: Using transient transfection studies in human dermal fibroblasts and the MCC cell line MCC13, we compared the transcription activity of the early and late promoters of the most commonly described non-coding control region MCPyV variant and six other isolates containing specific mutation patterns. Results: Both the early and late promoters were significantly stronger in human dermal fibroblasts compared with MCC13 cells, and a different promoter strength between the MCPyV variants was observed. The expression of fulllength large T-antigen, a viral protein that regulates early and late promoter activity, inhibited early and late promoter activities in both cell lines. Nonetheless, a truncated large T-antigen, which is expressed in virus-positive MCCs, stimulated the activity of its cognate promoter. Conclusion: The promoter activities of all MCPyV variants tested was stronger in human dermal fibroblasts, a cell line that supports viral replication, than in MCC13 cells, which are not permissive for MCPyV. Truncated large Tantigen, but not full-length large T-antigen stimulated viral promoter activity. Whether, the difference in promoter strength and regulation by large T-antigen may affect the replication and tumorigenic properties of the virus remains to be determined.

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