Experimental infection of sheep with a recombinant ORFV strain has previously shown that the severity of epithelial hyperplasia and neovascularization correlates with the presence of the active vVEGF gene.33 We found that ORFV activates inflammation characterized by CD163+ macrophages, and increases host EGFR expression and IL-6 production, which might promote oncogenesis through synergistic action with vVEGF signaling. Here, CD163 is linked to infection.