Unit of Virus Host Cell Interactions (UVHCI),
UMI 3265, 6, rue Jules-Horowitz, BP 181, 38042 Grenoble cedex 9, France, Institut de recherche biomédicale des armées (Irba), unité de virologie,
24, avenue des Maquis-du-Grésivaudan, 38702 La Tronche, France
Poxviruses are distinguished from other DNA viruses by replicating exclusively in the cytoplasm of the infected host cell. Replication of the linear double-stranded DNA genome takes place in the perinuclear area, in cytoplasmic foci called viral factories. Poxvirus genome organization evolved in order to prevent the virus from being dependent on nuclear enzymes. Therefore, they encode most, if not all, of the proteins required for efficient replication of their genome. Some of these proteins are essential for virus growth (i.e., enzymes directly involved in DNA synthesis). In contrast, others are dispensable for virus propagation in cell culture (i.e., proteins involved in nucleotide metabolism). Most of our knowledge concerning poxvirus replication comes from studies performed on
vaccinia virus, the virus used as vaccine to eradicate smallpox more than 30 years ago. This article reviews our current knowledge of the molecular mechanisms governing poxvirus genome synthesis, with a particular focus on the viral proteins involved in this process. A working model for poxvirus DNA replication is also presented.