Cell Host & Microbe
Volume 19, Issue 6, 8 June 2016, Pages 775-787
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Article
Identifying the Target Cells and Mechanisms of Merkel Cell Polyomavirus Infection

https://doi.org/10.1016/j.chom.2016.04.024Get rights and content
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Highlights

  • Merkel cell polyomavirus (MCPyV) preferentially infects dermal fibroblasts in human skin

  • Induction of MMPs by growth factors and WNT signaling stimulates MCPyV infection

  • Dermal fibroblasts represent a cell culture model supporting the full MCPyV life cycle

  • FDA-approved kinase inhibitor trametinib efficiently blocks MCPyV infection

Summary

Infection with Merkel cell polyomavirus (MCPyV) can lead to Merkel cell carcinoma (MCC), a lethal form of skin cancer. However, the skin cell type productively infected by MCPyV remains a central question. We combined cell culture and ex vivo approaches to identify human dermal fibroblasts as natural host cells that support productive MCPyV infection. Based on this, we established a cell culture model for MCPyV infection, which will facilitate investigation of the oncogenic mechanisms for this DNA virus. Using this model, we discovered that induction of matrix metalloproteinase (MMP) genes by the WNT/β-catenin signaling pathway and other growth factors stimulates MCPyV infection. This suggests that MCC risk factors such as UV radiation and aging, which are known to stimulate WNT signaling and MMP expression, may promote viral infection and thus drive MCC. Our study also introduces the FDA-approved MEK antagonist trametinib as an effective inhibitor for controlling MCPyV infection.

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