ubiquitous virus and infection commonly occurs during childhood but remains asymptomatic throughout an individual's lifetime. MCC was first believed to be associated with MCV when it was observed to occur at a much higher rate in HIV patients during the 1980s. Since then, studies have demonstrated integration of the MCV genome into the genome of MCC tumor cells. Central to the our understanding of the pathogenicity of MCV are two viral proteins expressed in infected cells known as the large tumor antigen (LT) and small tumor antigen (sT). Normally, patients infected with MCV show low levels of antibodies to the LT protein, perhaps due to a nuclear localization domain in its C-terminal that limits its cellular dispersion. However, integration of the viral genome into the host genome can result in truncation of the LT protein proximal to this domain. This serves two oncogenic purposes: first, it prevents successful viral replication that would culminate in lysis of the infected cell. Second, it redistributes the LT protein to the cytoplasm, where it can interact with cytoplasmic signaling. The N-terminal LXCXE motif of the LT protein has been shown to interact with known oncogene Rb and is conserved in other cancer-causing viruses. Studies suggest that LT may also preserve cell proliferation signals such as c-Myc and cyclin E and cause DNA injury to the p53 tumor suppressor. Meanwhile, sT has been shown to induce cell proliferation through hyper-phosphorylation of the translation initiator 4EBP1 as well as inhibition of a ubiquitin ligase complex responsible for degradation of cellular proliferation signals. sT also contains a region known as the LT stabilization domain (LSD), which potentiates the LT protein's oncogenic function. Unlike LT, MCC samples have been identified that express sT alone, and sT expression in fibroblasts has been shown to cause MCC phenotype development. UV light About 20% of MCC tumors are MCV negative. In contrast to MCV-induced MCC, these tumors tend to have much higher mutational burdens with mutational signatures characteristic of UV damage. Genes frequently mutated in MCV-negative MCC include p53 and Rb, among others. The link between MCC and UV exposure has been demonstrated through various epidemiological studies indicating a higher incidence of MCC in fair-skinned people in areas of high UV exposure, as well as among those receiving UV phototherapy. The typical distribution of MCC in sun-exposed regions and its co-occurrence with other skin cancers also indicate that UV exposure is