On infection of host cells, VV replication occurs rapidly to produce two infectious forms of virion: the IMV, retained within the cell until lysis, and an enveloped form that either remains attached to the cell surface as cell enveloped virus (CEV) or is released from the cell surface as EEV, a critical form for local and distant cell to cell spread.32 33 Functional analysis has demonstrated that while the VV B5R protein is required for formation of EEV, mutant viruses lacking the SCR domains within the protein actually produce more EEV. Here, CYB5R3 is linked to infection.