BioCentury
ARTICLE | Distillery Techniques

Techniques: Human cell model of Merkel cell polyomavirus infection

May 26, 2016 7:00 AM UTC

A human cell-based model could be useful for screening therapies to treat Merkel cell carcinoma, a form of skin cancer caused by the Merkel cell polyomavirus. A screen of multiple human skin cell types identified dermal fibroblasts as the primary type infected by the virus. The cell-based model involved culturing primary human dermal fibroblasts with epidermal growth factor, fibroblast growth factor (FGF) and a glycogen dependent kinase 3 (GSK3) inhibitor to enhance viral infectivity, then infecting the cells with recombinant Merkel cell polyomavirus to probe viral transcription and virion replication, or with a pseudovirus expressing GFP to visualize cell entry. In the model, Mekinist trametinib inhibited viral transcription and/or replication but not cell entry, whereas Imbruvica ibrutinib and Zydelig idelalisib had no detectable effect on viral infection. Next steps include using results from the cell-based model to develop an animal model to study how Merkel cell polyomaviral infection leads to Merkel cell carcinoma.

Novartis AG and Japan Tobacco Inc. market Mekinist, an inhibitor of MAP kinase kinase 1 (MAP2K1; MEK1) and MAP2K2 (MEK2), to treat melanoma...