DELETION OF THE VACCINIA VIRUS GROWTH-FACTOR GENE REDUCES VIRUS VIRULENCE
DELETION OF THE VACCINIA VIRUS GROWTH-FACTOR GENE REDUCES VIRUS VIRULENCE
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DOI：
10.1128/jvi.62.3.866-874.1988
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发表时间：
1988-03-01
影响因子：
5.4
通讯作者：
MOSS, B
中科院分区：
文献类型：
--
作者：
BULLER, RML;CHAKRABARTI, S;MOSS, B
痘苗病毒生长因子(VGF)基因编码一种氨基酸序列与表皮生长因子(EGF)和转化生长因子α同源的多肽，存在两次，一次出现在病毒基因组的两端，一次在病毒基因组的反向末端重复。重组程序被用β-半乳糖苷酶盒取代了两个VGF基因的一半以上，该盒用作分离无条件存活的VGF突变体的颜色指示剂。经Southern印迹分析和功能性生长因子检测，证实了VGF突变型和表型。在含有低密度或高密度EGF受体的各种细胞类型中，VGF病毒和野生型(WT)病毒的空斑形成效率相似，这表明在病毒感染的启动过程中对VGF或EGF受体缺乏特定的要求。在生长的BS-C-1和Swiss 3T3细胞中，VGF-病毒的产量与WT病毒相似，但在静止的Swiss 3T3细胞中产量较低。VGF-病毒和WT病毒在体内的最大区别是：对小鼠的颅内致死和对兔皮肤病变的产生需要比WT病毒更高剂量的VGF-病毒。因此，VGF基因的表达对痘苗病毒的毒力具有重要意义。
The vaccinia virus growth factor (VGF) gene encodes a polypeptide with amino acid sequence homology to epidermal growth factor (EGF) and transforming growth factor alpha and is present twice, once at each end of the virus genome within the inverted terminal repetition. Recombination procedures were used to replace more than half of both VGF genes with a .beta.-galactosidase cassette which served as a color indicator for isolating an unconditionally viable VGF- mutant. The VGF- mutant genotype and phenotype were confirmed by Southern blot analysis and assays for functional growth factor. The plaque-forming efficiencies of VGF- and wild-type (WT) viruses were similar in a variety of cell types containing low or high densities of EGF receptors, suggesting a lack of a specific requirement for either VGF or the EGF receptor in the initiation of virus infection. The yield of VGF- virus was similar to that of WT virus in growing BS-C-1 and Swiss 3T3 cells, but lower in resting Swiss 3T3 cells. The greatest differences between VGF- and WT virus occurred in vivo: higher doses of VGF- virus than WT virus were required for intracranial lethality in mice and for production of skin lesions in rabbits. Thus, expression of the VGF gene is important to the virulence of vaccinia virus.