Effect of 3-beta-hydroxysteroid dehydrogenase gene deletion on virulence and immunogenicity of different vaccinia viruses and their recombinants.
3-beta-Hydroxysteroid dehydrogenase (3-beta-HSD) activity coded for by the A44L gene of vaccinia virus (VV) was demonstrated in CV-1 cultures infected by all five VV strains tested, viz. WR, Praha virus, DRYVAX Wyeth-derived virus (DD), LIVP and MVA. Deletion of the A44L gene in two Praha virus-derived clones (the moderately virulent P13 and the highly attenuated P20), the WR and DD viruses resulted in absence of 3-beta-HSD activity from infected cultures. The virulence for mice of P13 was not affected, and that of WR was only slightly decreased, by the A44L gene deletion. Recombinant VVs expressing either varicella-zoster virus glycoprotein E (VZV-gE) or hepatitis B virus preS2-S protein (HBV-preS2-S) and their respective A44L deleted mutants were used in immunogenicity tests in mice. In terms of antibody response to VV and the recombinant proteins, the deletion resulted in a lowering the immunogenicity in the moderately virulent clone P13 virus and its progenies. In the highly attenuated P20 and DD viruses and their progenies no effects were apparent.
Institute of Hematology and Blood Transfusion, Praha, Czech Republic.
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V
Sroller
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L
Kutinová
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S
Nĕmecková
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V
Simonová
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V
Vonka
D015096:3-Hydroxysteroid Dehydrogenases / Q000235:genetics*; D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis; D002460:Cell Line; D017931:DNA Primers / Q000235:genetics; D004279:DNA, Viral / Q000235:genetics / Q000302:isolation & purification; D017353:Gene Deletion; D005814:Genes, Viral; D007114:Immunization; D051379:Mice; D008807:Mice, Inbred BALB C; D008813:Mice, Inbred ICR; D009693:Nucleic Acid Hybridization; D016133:Polymerase Chain Reaction; D051381:Rats; D011995:Recombination, Genetic; D013045:Species Specificity; D014616:Vaccinia virus / Q000201:enzymology* / Q000235:genetics* / Q000472:pathogenicity; D014774:Virulence / Q000235:genetics
D000914:Antibodies, Viral; D017931:DNA Primers; D004279:DNA, Viral; D015096:3-Hydroxysteroid Dehydrogenases