A HSV1 mutant leads to an attenuated phenotype and induces immunity with a protective effect
A HSV1 mutant leads to an attenuated phenotype and induces immunity with a protective effect
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HSV1突变体导致表型减弱并诱导具有保护作用的免疫
DOI：
10.1371/journal.ppat.1008703
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发表时间：
2020
期刊：
影响因子：
6.7
通讯作者：
Li Qihan
中科院分区：
文献类型：
--
作者：
Xu Xingli;Feng Xiao;Wang Lichun;Yi Ting;Zheng Lichun;Jiang Guorun;Fan Shengtao;Liao Yun;Feng Min;Zhang Ying;Li D;an;Li Qihan
1型单纯疱疹病毒（HSV1）是一种结构复杂的病毒，具有复杂的转录过程和高感染率。迫切需要针对 HSV1 的疫苗。由于多种病毒编码蛋白（包括结构蛋白和非结构蛋白）有助于刺激免疫反应，因此减毒或缺陷型 HSV1 疫苗可能相对可靠。基因组修饰技术的进步为构建各种 HSV 候选疫苗提供了可靠的方法。基于我们之前的工作，建立了 UL7、UL41、LAT、Us3、Us11 和 Us12 基因突变的 M6 突变体。该突变体在动物模型中表现出细胞增殖低和表型减弱。此外，在小鼠和恒河猴中，该突变体可以诱导显着的血清中和抗体滴度和 T 细胞活化，并通过阻止病毒复制、传播和发病机制来防止 HSV1 攻击。
Herpes simplex virus type 1 (HSV1) is a complicated structural agent with a sophisticated transcription process and a high infection rate. A vaccine against HSV1 is urgently needed. As multiple viral-encoded proteins, including structural and nonstructural proteins, contribute to immune response stimulation, an attenuated or deficient HSV1 vaccine may be relatively reliable. Advances in genomic modification technologies provide reliable means of constructing various HSV vaccine candidates. Based on our previous work, an M6 mutant with mutations in the UL7, UL41, LAT, Us3, Us11 and Us12 genes was established. The mutant exhibited low proliferation in cells and an attenuated phenotype in an animal model. Furthermore, in mice and rhesus monkeys, the mutant can induce remarkable serum neutralizing antibody titers and T cell activation and protect against HSV1 challenge by impeding viral replication, dissemination and pathogenesis.