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基因工程单纯疱疹病毒R7017和R7020的体内行为:在啮齿动物中的构建与评估

In vivo behavior of genetically engineered herpes simplex viruses R7017 and R7020: construction and evaluation in rodents.

作者信息

Meignier B, Longnecker R, Roizman B

机构信息

Institut Mérieux, Marcy l'Etoile, France.

出版信息

J Infect Dis. 1988 Sep;158(3):602-14. doi: 10.1093/infdis/158.3.602.

DOI:10.1093/infdis/158.3.602
PMID:2842408
Abstract

The herpes simplex virus (HSV) recombinant R7017 was constructed from HSV-1 (strain F) by deleting a portion of the thymidine kinase (tk) gene and by replacing the sequences representing the internal inverted repeats and adjacent genes in the L component with a fragment of the HSV-2 genome encoding the glycoproteins G, D, I, and a portion of E. In addition, the R7020 recombinant contains an HSV-1 DNA fragment encoding the tk gene fused to the alpha 4 gene promoter. The results of studies in mice, guinea pigs, and rabbits were as follows: Both recombinants remained unchanged after nine serial, intracerebral passages in mice; the recombinants could not be differentiated with respect to attenuation in mice injected intracerebrally, in vaginally infected guinea pigs, and in rabbits inoculated on the scarified cornea. Given intradermally or intramuscularly, the recombinants prevented severe infections by virulent challenge viruses, and R7020 established latent infections (at a low frequency) in all species tested, whereas latent R7017 virus was detected in rabbits only.

摘要

单纯疱疹病毒(HSV)重组体R7017是由HSV - 1(F株)构建而成,构建方法是删除胸苷激酶(tk)基因的一部分,并将L成分中代表内部反向重复序列和相邻基因的序列,用编码糖蛋白G、D、I以及部分E的HSV - 2基因组片段替换。此外,R7020重组体包含一个编码tk基因的HSV - 1 DNA片段,该片段与α4基因启动子融合。在小鼠、豚鼠和兔子身上的研究结果如下:两种重组体在小鼠脑内连续传代九次后均未发生变化;在脑内注射的小鼠、阴道感染的豚鼠以及接种于划痕角膜的兔子中,无法区分这两种重组体在减毒方面的差异。经皮内或肌肉注射后,这两种重组体可预防强毒攻击病毒引起的严重感染,并且R7020在所有受试物种中均能(以低频率)建立潜伏感染,而潜伏的R7017病毒仅在兔子中被检测到。

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