HERPES-SIMPLEX VIRUS-1 GAMMA(1)34.5-GENE FUNCTION, WHICH BLOCKS THE HOST RESPONSE TO INFECTION, MAPS IN THE HOMOLOGOUS DOMAIN OF THE GENES EXPRESSED DURING GROWTH ARREST AND DNA-DAMAGE
HERPES-SIMPLEX VIRUS-1 GAMMA(1)34.5-GENE FUNCTION, WHICH BLOCKS THE HOST RESPONSE TO INFECTION, MAPS IN THE HOMOLOGOUS DOMAIN OF THE GENES EXPRESSED DURING GROWTH ARREST AND DNA-DAMAGE
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DOI：
10.1073/pnas.91.12.5247
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发表时间：
1994-06-07
影响因子：
11.1
通讯作者：
ROIZMAN, B
中科院分区：
文献类型：
--
作者：
CHOU, J;ROIZMAN, B
单纯疱疹病毒的Gamma(1)34.5基因在某些细胞系(如Vero)中是必不可少的。在其他细胞中(例如，人神经母细胞瘤细胞系SK-N-SH)，伽马(1)34.5(-)缺失突变体会触发所有蛋白质合成的过早完全停止，从而使细胞无法存活，并显著减少病毒产量。无法阻止导致感染细胞死亡的细胞应激反应可能是缺失突变体无法繁殖并导致小鼠中枢神经系统病理的原因。Gamma(1)34.5基因由一个氨基末端结构域、一个由3个氨基酸重复5-10次组成的可变连接区和一个与MyD116的相应结构域同源的羧基末端结构域组成，MyD116是在白介素6的诱导下在髓系白血病细胞中表达的分化基因，而生长停滞和DNA损伤基因34(Gadd34)是由生长停止和DNA损伤诱导的基因。我们已经构建了几个病毒突变体，从这些突变体中，伽马(1)34.5基因的各个结构域被删除或通过插入终止密码子而变得沉默。对这些突变体的研究表明，阻止蛋白质合成完全停止所需的Gamma(1)34.5基因结构域对应于Gamma(1)34.5基因的羧基末端结构域，与MyD116和Gadd34基因的相应编码域同源。
The gamma(1)34.5 gene of herpes simplex virus is dispensable in some cell lines (e.g., Vero). In others (e.g., human neuroblastoma cell line SK-N-SH), the gamma(1)34.5(-) deletion mutant triggers a premature total shutoff of all protein synthesis, thereby rendering the cell nonviable and reducing drastically viral yields. The inability to prevent the cellular stress response that causes the infected cell to die may be responsible for the inability of the deletion mutant to multiply and cause pathology in the central nervous system of mice. The gamma(1)34.5 gene consists of an amino-terminal domain, a variable linker sequence consisting of 3 amino acids repeated 5-10 times, and a carboxyl-terminal domain homologous to the corresponding domain of MyD116, a gene expressed in myeloid leukemia cells induced to differentiate by interleukin 6, and growth arrest and DNA damage gene 34 (GADD34), a gene induced by growth arrest and DNA damage. We have constructed several viral mutants from which various domains of the gamma(1)34.5 gene had been deleted or rendered mute by the insertion of a stop codon. Studies on those mutants show that the domain of the gamma(1)34.5 gene necessary to preclude the total shutoff of protein synthesis corresponds to the carboxyl-terminal domain of the gamma(1)34.5 gene homologous to the corresponding coding domain of the MyD116 and GADD34 genes.