Department of Virology 1, National Institute of Infectious Diseases, Japan.
Department of Developmental Medical Sciences, The University of Tokyo, Japan.
Jpn J Infect Dis. 2022 Jul 22;75(4):368-373. doi: 10.7883/yoken.JJID.2021.674. Epub 2021 Dec 28.
Herpes simplex virus 1 (HSV-1)-TK (8UAG) expresses a truncated thymidine kinase (TK) translated from the second initiation codon due to a stop codon (UAG) at the 8th position (counted from the first initiation codon). Here, we showed that the sensitivity of HSV-1-TK (8UAG) to acyclovir (ACV) is similar to that of the control HSV-1 wild-type (WT), which expresses an intact TK protein. However, HSV-1-TK (44UAG), which expresses a truncated TK due to a UAG codon at position 44, showed lower sensitivity to ACV. A mouse infection model was used to compare the virulence of HSV-1-TK (8UAG) and HSV-1-TK (44UAG) to that of HSV-1 WT. The 50% lethal dose (LD) for HSV-1-TK (44UAG) was 7.8-fold higher than that for HSV-1-TK (8UAG), whereas the LD for HSV-1-TK (8UAG) was the same as that for the parental HSV-1 WT. There were no statistically significant differences among HSV-1-TK (44UAG), HSV-1-TK (8UAG), and HSV-1 WT with respect to replication capacity and viral TK mRNA expression in the mouse brain. Thus, the virulence of HSV-1 expressing the truncated viral TK translated from the second initiation codon might depend on the position of the UAG stop codon.
单纯疱疹病毒 1（HSV-1）-TK（8UAG）表达一种截断的胸苷激酶（TK），该 TK 由第二个起始密码子翻译而来，因为在第 8 位（从第一个起始密码子开始计数）存在一个终止密码子（UAG）。在这里，我们表明 HSV-1-TK（8UAG）对阿昔洛韦（ACV）的敏感性与表达完整 TK 蛋白的对照 HSV-1 野生型（WT）相似。然而，由于位置 44 的 UAG 密码子，表达截断 TK 的 HSV-1-TK（44UAG）对 ACV 的敏感性较低。使用小鼠感染模型比较了 HSV-1-TK（8UAG）和 HSV-1-TK（44UAG）与 HSV-1 WT 的毒力。HSV-1-TK（44UAG）的 50%致死剂量（LD）比 HSV-1-TK（8UAG）高 7.8 倍，而 HSV-1-TK（8UAG）的 LD 与亲本 HSV-1 WT 相同。HSV-1-TK（44UAG）、HSV-1-TK（8UAG）和 HSV-1 WT 在小鼠脑中的复制能力和病毒 TK mRNA 表达方面没有统计学上的显著差异。因此，表达从第二个起始密码子翻译而来的截断病毒 TK 的 HSV-1 的毒力可能取决于 UAG 终止密码子的位置。
