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 3 beta-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.
Moore
J B
JB
Sir William Dunn School of Pathology, University of Oxford, England.
Smith
G L
GL
D015096:3-Hydroxysteroid Dehydrogenases / Q000235:genetics* / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D015139:Blotting, Southern; D002478:Cells, Cultured; D004279:DNA, Viral / Q000235:genetics; D005814:Genes, Viral; D006728:Hormones / Q000096:biosynthesis*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D016366:Open Reading Frames; D011233:Precipitin Tests; D012333:RNA, Messenger / Q000235:genetics; D013256:Steroids / Q000096:biosynthesis*; D014158:Transcription, Genetic; D014616:Vaccinia virus / Q000201:enzymology* / Q000235:genetics / Q000472:pathogenicity; D014774:Virulence / Q000235:genetics
D004279:DNA, Viral; D006728:Hormones; D012333:RNA, Messenger; D013256:Steroids; D015096:3-Hydroxysteroid Dehydrogenases