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Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Cell+Host+Microbe 2016 ; 19 (6): 775-87 Nephropedia Template TP
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Identifying the target cells and mechanisms of Merkel cell polyomavirus infection #MMPMID27212661
Liu W; Yang R; Payne AS; Schowalter RM; Spurgeon ME; Lambert PF; Xu X; Buck CB; You J
Cell Host Microbe 2016[Jun]; 19 (6): 775-87 PMID27212661show ga
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/?-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.