STEROID-HORMONE SYNTHESIS BY A VACCINIA ENZYME - A NEW TYPE OF VIRUS VIRULENCE FACTOR

Vaccinia virus open reading frame (ORF) SalF7L has 31% amino acid identity to human 30-hydroxysteroid dehydrogenase/DELTA-5-DELTA-4 isomerase (3-beta-HSD). Here we show that SalF7L encodes an active 3-beta-HSD, by the conversion of pregnenolone to the steroid hormone progesterone. The gene is transcribed early during infection into a 1.4 kb mRNA from an initiation site 12 bp upstream of the ORF. An antiserum raised against bacterially expressed SalF7L immunoprecipitated a 38 kDa polypeptide from infected cells, but not from mock infected cells or from cells infected with a mutant virus from which the SalF7L ORF had been removed. Deletion of the gene had no effect on virus replication in CV-1 cells in culture, yet the deletion mutant was attenuated when intranasally inoculated into mice. This steroid hormone synthesizing enzyme is a novel type of virus virulence factor.