The role of the UL41 gene of herpes simplex virus type 1 in evasion of non-specific host defence mechanisms during primary infection
The role of the UL41 gene of herpes simplex virus type 1 in evasion of non-specific host defence mechanisms during primary infection
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DOI：
10.1099/0022-1317-81-7-1763
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发表时间：
2000-07-01
影响因子：
3.8
通讯作者：
Azuma, M
中科院分区：
文献类型：
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作者：
Suzutani, T;Nagamine, M;Azuma, M
单纯疱疹病毒UL41基因产物(VHS)被包裹在病毒粒子中，在病毒复制周期的早期介导宿主蛋白质合成的停止。为了阐明VHS在病毒复制和毒力中的作用，我们分离到了一个完全缺乏UL41的突变株(VR Delta 41株)及其回复株(VR Delta 41R株)。在小鼠脑炎模型中，VR Delta 41株在感染后2天被淋巴细胞和/或中性粒细胞等伽玛射线敏感细胞抑制复制，导致毒力低下。在VR Delta 41接种的大脑中产生，激活并诱导伽马射线敏感细胞迁移到感染部位。因此，我们对单纯疱疹病毒L感染的人细胞产生的细胞因子进行了筛选，并观察到VR Delta 41感染能有效诱导IL-1β、IL-8和巨噬细胞炎性蛋白-1α的产生，并且VR Delta 41株对干扰素-α和-β的敏感性分别是野生型的20倍和5倍。这些结果表明，VHS在体内的一个重要作用是通过抑制HSV感染细胞中细胞因子的产生和降低干扰素-α和-β的抗HSV活性来逃避初次感染时的非特异性宿主防御机制。
The UL41 gene product (vhs) of herpes simplex virus (HSV) is packaged in the virion, and mediates host protein synthesis shutoff at the early stage of the virus replication cycle, In order to clarify the role of vhs in virus replication and virulence, we isolated a completely UL41-deficient mutant (the VR Delta 41 strain) and its revertant (the VR Delta 41R strain), In the mouse encephalitis model, the replication of strain VR Delta 41 was inhibited after 2 days post-infection, resulting in low virulence, by gamma-ray-sensitive cells such as lymphocytes and/or neutrophils, The result suggested that some cytokines, produced in VR Delta 41-inoculated brains, activate and induce the migration of gamma-ray-sensitive cells to the infection site. Therefore, cytokines produced by HSV-l-infected human cells were screened, and potent inductions of interleukin (IL)-1 beta, IL-8 and macrophage inflammatory protein-1 alpha by VR Delta 41 infection were observed, Moreover, the VR Delta 41 strain showed 20- and 5-fold higher sensitivity to interferon-alpha and -beta compared to the wild-type strain, respectively. These results indicate that one important role of vhs in vivo is evasion from non-specific host defence mechanisms during primary infection through suppression of cytokine production in HSV-infected cells and reduction of the anti-HSV activity of interferon-alpha and -beta.