Ricerc@Sapienza

Merkel cell polyomavirus (MCPyV) is a double-stranded DNA virus that has been associated with a rare but aggressive skin cancer, Merkel cell carcinoma (MCC). Two characteristics of MCPyV¿positive MCCs are integration of the viral genome and expression of a truncated version of large T antigen (LT). Considering the well described role of MCPyV in the development of MCC and the widespread prevalence of the virus across the body, the involvement of MCPyV in tumours other than MCC remains to establish. It has been proposed that MCPyV may be associated with some types of non-MCC cancers and several studies reported the frequently detection of MCPyV DNA or transcripts at a varying level in healthy respiratory tissue and in cancer lung tissue. However, many of these examples are not able to clearly demonstrate a direct connection between cellular transformation and the presence of the virus. Since mechanistic studies to fully investigate MCPyV molecular biology and oncogenic mechanisms in malignancies, other than MCC, have been hampered by a lack of adequate cell culture model, a pulmonary cell culture infection system for MCPyV will be established. Building on this model we will focus on the biology of MCPyV in respiratory system's cells and on its potential contribution to triggering a neoplastic transformation in these cells type. Specifically, the state of the viral genome (episomal or integrated) and the expression and contribution of LT and small T (sT) viral proteins to transformation and cancer growth in lung tumour will be determined. Moreover, in parallel, to further study the MCPyV biology and its oncogenic properties in lung tissue, lung organoid culture will be developed.