Thompson R L, Stevens J G
Virology. 1983 Nov;131(1):171-9. doi: 10.1016/0042-6822(83)90543-3.
In this study, a pre-existing "library" of Herpes Simplex Virus (HSV) intertypic recombinants was found to be not useful for mapping HSV genes controlling viral neurovirulence in mice. Most of these agents were significantly less virulent than either parental type following intracranial inoculation, and in the general case this lessened virulence could be attributed to inefficient replication in any cell type at 38.5 degrees (the normal temperature of the mouse). One agent tested (recombinant RE6) was completely non-neurovirulent following intracranial inoculation of as much as 3.2 X 10(7) PFU. Since about 10 PFU of either 17 Syn+ or HG52 (the "parental" strains of this recombinant) were lethal for mice, RE6 is at least 10 million-fold less neurovirulent than the wild-type strains from which it was produced. The function of the defective gene(s) in RE6 is not yet known, but it is not required for the expression of viral thymidine kinase, efficient replication in cultured cells at 38.5 degrees, or replication in non-neural mouse tissue in vivo. Therefore, the defect in RE6 is in an HSV gene function(s) which is absolutely required for neurovirulence but not for general viral replication. Several possibilities for the molecular nature of the defect in RE6 are discussed.
在本研究中，发现一个预先存在的单纯疱疹病毒（HSV）型间重组体“文库”对于定位控制小鼠病毒神经毒力的HSV基因并无用处。在颅内接种后，这些重组体中的大多数毒力明显低于任何一种亲代病毒类型，一般来说，这种毒力降低可归因于在38.5摄氏度（小鼠的正常体温）时在任何细胞类型中的复制效率低下。测试的一种重组体（重组体RE6）在颅内接种多达3.2×10⁷ 空斑形成单位（PFU）后完全无神经毒力。由于17 Syn⁺ 或HG52（该重组体的“亲代”菌株）约10 PFU对小鼠是致死性的，RE6的神经毒力比产生它的野生型菌株至少低1000万倍。RE6中缺陷基因的功能尚不清楚，但它对于病毒胸苷激酶的表达、在38.5摄氏度的培养细胞中的高效复制或在体内非神经小鼠组织中的复制并非必需。因此，RE6的缺陷在于HSV的一种基因功能，这种功能对于神经毒力是绝对必需的，但对于一般病毒复制并非必需。文中讨论了RE6缺陷分子性质的几种可能性。
