Large T and small T antigens of Merkel cell polyomavirus

•Merkel cell polyomavirus (MCV) is a newly discovered human tumor virus that causes Merkel cell carcinoma (MCC).•MCV is clonally integrated in MCC tumor cells.•Large T antigens carry signature C-terminal truncations in MCC.•MCV-associated tumorigenesis is characterized by the expression of LT and sT antigens.•Functional domains and motifs of LT and sT mediate MCV tumorigenesis.

Merkel cell polyomavirus (MCV) is the etiological agent of Merkel cell carcinoma (MCC), a rare and highly lethal human skin cancer. A natural component of skin flora, MCV becomes tumorigenic only after integration into the host DNA together with specific mutations to the viral genome. Research on MCV large T (LT) and small T (sT) antigens, the only viral products expressed in MCC, shows that these major oncoproteins not only possess biochemical functions found in common with other polyomavirus T antigens, but also demonstrate new cellular targets not described in previous polyomavirus models. This review provides a map of the relevant functional motifs and domains in MCV T antigens that have been identified, highlighting their roles in tumorigenesis.