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Considering the fact that this virus is large and complex, replication is relatively quick taking approximately 12 hours until the host cell dies by the release of viruses.

After the genome has been replicated, the immature virion (IV) assembles the A5 protein to create the intracellular mature virion (IMV).They vary in their shape depending upon the species but are generally shaped like a brick or as an oval form similar to a rounded brick because they are wrapped by the endoplasmic reticulum.The virion is exceptionally large, its size is around 200 nm in diameter and 300 nm in length and carries its genome in a single, linear, double-stranded segment of DNA.A second clade included both alastrim minor (a phenotypically mild smallpox) described from the American continents and isolates from West Africa which diverged from an ancestral strain between 1,400 and 6,300 years before present.This clade further diverged into two subclades at least 800 years ago.

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