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

STEROID-HORMONE SYNTHESIS BY A VACCINIA ENZYME - A NEW TYPE OF VIRUS VIRULENCE FACTOR
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DOI:
10.1002/j.1460-2075.1992.tb05251.x
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发表时间:
1992-05-01
期刊:
影响因子:
11.4
通讯作者:
SMITH, GL
SMITH, GL
中科院分区:
生物学1区
文献类型:
--
作者:
MOORE, JB;SMITH, GL

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痘苗病毒开放阅读框 (ORF) SalF7L 与人 30-羟基类固醇脱氢酶/DELTA-5-DELTA-4 异构酶 (3-β-HSD) 具有 31% 的氨基酸同一性。在这里,我们表明 SalF7L 通过将孕烯醇酮转化为类固醇激素孕酮来编码活性 3-β-HSD。该基因在感染早期从 ORF 上游 12 bp 的起始位点转录成 1.4 kb mRNA。针对细菌表达的 SalF7L 产生的抗血清可免疫沉淀来自感染细胞的 38 kDa 多肽,但不能从模拟感染细胞或感染已去除 SalF7L ORF 的突变病毒的细胞中免疫沉淀。该基因的删除对培养的 CV-1 细胞中的病毒复制没有影响,但当鼻内接种到小鼠体内时,删除突变体被减弱。这种类固醇激素合成酶是一种新型病毒毒力因子。
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.