ISOLATION AND CHARACTERIZATION OF ATTENUATED MUTANTS OF VACCINIA VIRUS
ISOLATION AND CHARACTERIZATION OF ATTENUATED MUTANTS OF VACCINIA VIRUS
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DOI：
10.1016/0042-6822(87)90480-6
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发表时间：
1987-08-01
期刊：
影响因子：
3.7
通讯作者：
ESTEBAN, M
中科院分区：
文献类型：
--
作者：
DALLO, S;ESTEBAN, M
通过长期感染Friend红白血病（FEL）细胞，获得了具有两个特异性和稳定遗传标记的减毒痘苗病毒变体。遗传标记是病毒基因组左侧HindIII-C末端的8-MDa缺失和HindIII-A DNA片段中部的序列改变。后一种遗传标记导致这些变体的小斑块大小表型。分析了这些变体在组织培养细胞中的复制模式及其对小鼠的毒力。在培养的细胞中，这些变体大大降低了不同来源细胞系中的病毒产量。这些变异体渗透到细胞中，合成早期和晚期病毒蛋白，并以与野生型病毒相同的效率复制它们的DNA。这些变异体的缺陷出现在病毒成熟过程中的某个步骤。当用这些变体腹膜内（ip）接种BALB/c小鼠组时，50%的小鼠存活，1倍。109空斑形成单位（PFU），而接种1 ×106 PFU野生型病毒。当用致死剂量的野生型病毒ip攻击时，用这些变体接种的小鼠得到完全保护。这些变体的毒力降低与8-MDa缺失相关;此外，空斑大小表型标记有助于进一步降低牛痘病毒的毒力。由于它们有限的病毒生产和保护性免疫应答，这些变体可能作为疫苗潜在有用。
Attenuated variants of vaccinia virus with two specific and stable genetic markers were obtained after long-term passage of persistently infected Friend erythroleukemia (FEL) cells. The genetic markers were an 8-MDa deletion on the left HindIII-C terminus of the viral genome and sequence alterations localized in the middle of the HindIII-A DNA fragment. This latter genetic marker led to small plaque size phenotype of these variants. The mode of replication of these variants in tissue culture cells and their virulence in mice were analyzed. In cultured cells, these variants have greatly reduced virus yields in cell lines of different origins. These variants penetrate into cells, synthesize early and late viral proteins, and replicate their DNA with about the same efficient as wild-type virus. The defect of these variants appears at some step during virus maturation. When groups of BALB/c mice were inoculated intraperitoneally (ip) with these variants, 50% of the mice survived with .gtoreq. 1 .times. 109 plaque-forming units (PFU) as opposed to about 50% survival for mice inoculated with 1 .times. 106 PFU of wild-type virus. Mice inoculated with these variants were fully protected when challenged ip with lethal doses of wild-type virus. The reduced virulence of these variants correlated with the 8-MDa deletion; in addition, the plaque size phenotype marker contributes to a further decrease of the virulence of vaccinia virus. Due to their limited virus production and protective immune response, these variants may be potentially useful as vaccines.