MCPyV gene expression in infection and MCC. A) MCPyV genomic map. The NCRR contains the origin of replication and bidirectional promoters, which drive the expression of the viral early genes (right) and late genes (left). B) The MCPyV genome is maintained as a replication-competent episome in persistently infected cells, which expresses the early and late viral genes in a temporal manner. In MCPyV-positive MCC, the MCPyV genome is clonally integrated in the host cell genome. Integrated MCPyV continues to express sT and a truncated LT (LTT) that preserve the expression of the N-terminal LXCXE Rb-binding domain but not the C terminal domains needed for regulating viral replication. The LTT truncation mutations and the lack of late gene expression in MCC are denoted by gray Xs. Abbreviations: NCRR, noncoding regulatory region; EP, early promoter; LP, late promoter; LT, large tumor antigen; sT, small tumor antigen; 57 kT, 57 kDa tumor antigen; ALTO, alternate large tumor antigen open reading frame; LTT, truncated large tumor antigen.