Fig. 1.

Schematic overview of the MVA life cycle and important virus proteins to overcome intracellular host restrictions in human cells. As all poxviruses, MVA replicates in the cytoplasm of infected cells. Following entry, the virus replication comprises three steps of viral RNA and protein synthesis defined as expression of early, intermediate, and late viral genes. Production and processing of late structural proteins result in the morphogenesis of new infectious virions enveloped by one or two additional lipid membranes. Depicted are five early viral proteins needed to complete the MVA life cycle. The VACV proteins B18, C7, and E3 are conserved in MVA; interfere with different host restriction targets (including SAMD9, PKR, and unknown); and are important to maintain viral uncoating, DNA replication, and postreplicative gene expression in human cells. VACV C12 and C16 are the additional host-range proteins needed to rescue full MVA replicative capacity in human cells through association with host restrictions interfering with viral late protein processing, assembly, and morphogenesis (targets include FAM111A and unknown).