Ectromelia virus growth factor is not secreted from infected cells and plays no apparent role for virus replication in vitro.

Many poxviruses of vertebrates express proteins related to epidermal growth factor (EGF). We recently reported that recombinant ectromelia virus growth factor (ECGF) acts as a bona fide mitogen when added to cultured cells. Additionally, while most GF proteins from other related orthopoxviruses contain a transmembrane domain, ECGF lacks this region and, as such, should be directly released without the need for proteolytic processing at the plasma membrane. However, we could not detect secreted ECGF from virus-infected cells in vitro using an indirect functional assay; in contrast, we readily observed secreted GFs in the culture media from vaccinia and cowpox virus-infected cells. Furthermore, ectromelia virus lacking its ECGF gene (ECTVΔECGF) displayed equivalent in vitro replication compared to wild-type virus in various cell lines derived from mammalian species. It remains unclear why a seemingly functional ECGF remains in the genome of ECTV when it does not appear to be released from infected cells and has no obvious role for virus replication. Perhaps this protein maintains a role for viral fitness in vivo - future studies need to address this possibility.