Merkel Cell Polyomavirus: Oncogenesis in a Stable Genome

Merkel cell polyomavirus (MCV) is the causative agent for the majority of Merkel cell carcinoma (MCC) cases. Polyomavirus-associated MCC (MCCP) is characterized by the integration of MCV DNA into the tumor genome and a low tumor mutational burden. In contrast, nonviral MCC (MCCN) is characterized by a high tumor mutational burden induced by UV damage. Since the discovery of MCV, much work in the field has focused on understanding the molecular mechanisms of oncogenesis driven by the MCV tumor (T) antigens. Here, we review our current understanding of how the activities of large T (LT) and small T (ST) promote MCC oncogenesis in the absence of genomic instability. We highlight how both LT and ST inhibit tumor suppressors to evade growth suppression, an important cancer hallmark. We discuss ST interactions with cellular proteins, with an emphasis on those that contribute to sustaining proliferative signaling. Finally, we examine active areas of research into open questions in the field, including the origin of MCC and mechanisms of viral integration.

Automated summary

This review summarizes the current understanding of the oncogenic mechanisms driven by Merkel cell polyomavirus (MCV) in Merkel cell carcinoma (MCC). The study focuses on the roles of large T (LT) and small T (ST) antigens in promoting MCC oncogenesis and evading growth suppression. The paper also highlights unresolved research questions regarding the origin of MCC and viral integration mechanisms.