About 200 proteins are encoded by the 200 kb genome of the poxvirus. It has covalently closed hairpin ends (no free 3' or 5' ends) and is a linear, double-stranded DNA genome. At both ends, it has 10 kilobyte inverted terminal repeats (ITR). Since intergenic sequences longer than 100 bp are uncommon, genes are tightly packed. The "housekeeping" genes involved in transcription, replication, and virion assembly are encoded in the core conserved area. The genes that are encoded in the terminal sections differ between different poxviruses and produce proteins implicated in disease and host range.

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