Immunomodulation by poxviruses: Insights into virus-host interactions by selectively deleting poxvirus genes

The Poxviridae encompass a nearly ubiquitous family of DNA viruses capable of infecting a broad spectrum of vertebrates (Chordopoxvirinae) and insects (Entomopoxvirinae)¹. The Chordopoxviruses in particular include several viruses of economic and social importance to humans, and thus are the most extensively studied and best characterized (Table 1). Poxviruses are notable among DNA viruses for their large virion size and the ability to replicate within the cytoplasm of infected cells autonomous of the host nuclear machinery. Poxviruses also possess one of the largest viral genomes, ranging in size from 135 kb to 290 kb and encoding as many as 260 open reading frames (ORFs). The poxvirus genome consists of linear doublestranded DNA characterized by termini that form covalently closed hairpin loops and flanking terminal inverted repeat (TIR) regions that contain varying numbers of genes whose positions and orientations are mirrored at the opposing ends of the genome (Figure 1)¹. In general, genes that are centrally located in the genome are conserved among poxviruses and have common essential molecular functions, such as replication and virion assembly.