Different members of the tetraspanin superfamily have been described to regulate different virus infectious cycles at several stages: viral entry, viral replication or virion exit or infectivity. In addition, tetraspanin CD81 regulates HIV reverse transcription through its association with the dNTP hydrolase SAMHD1. Here we aimed at analysing the role of CD81 in Herpes simplex virus 1 infectivity using a neuroblastoma cell model. For this purpose, we generated a CD81 KO cell line using the CRISPR/Cas9 technology. Despite being CD81 a plasma membrane protein, CD81 KO cells showed no defects in viral entry nor in the expression of early protein markers. In contrast, glycoprotein B and C, which require viral DNA replication for their expression, were significantly reduced in CD81 KO infected cells. Indeed, HSV-1 DNA replication and the formation of new infectious particles were severely compromised in CD81 KO cells. We could not detect significant changes in SAMHD1 total expression levels, but a relocalization into endosomal structures was observed in CD81 KO cells. In summary, CD81 KO cells showed impaired viral DNA replication and produced greatly diminished viral titers.

中文翻译：

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四跨膜蛋白 CD81 调节 HSV-1 感染。

四跨膜蛋白超家族的不同成员已被描述为在几个阶段调节不同的病毒感染周期：病毒进入、病毒复制或病毒体退出或感染性。此外，四跨膜蛋白 CD81 通过与 dNTP 水解酶 SAMHD1 的结合来调节 HIV 逆转录。在这里，我们的目的是使用神经母细胞瘤细胞模型分析 CD81 在单纯疱疹病毒 1 感染中的作用。为此，我们使用 CRISPR/Cas9 技术生成了 CD81 KO 细胞系。尽管 CD81 是质膜蛋白，但 CD81 KO 细胞在病毒进入和早期蛋白标记物的表达方面均未显示缺陷。相比之下，需要病毒DNA复制才能表达的糖蛋白B和C在CD81 KO感染的细胞中显着减少。事实上，HSV-1 DNA 复制和新感染性颗粒的形成在 CD81 KO 细胞中受到严重损害。我们无法检测到 SAMHD1 总表达水平的显着变化，但在 CD81 KO 细胞中观察到重新定位到内体结构。总之，CD81 KO 细胞表现出病毒 DNA 复制受损，产生的病毒滴度大大降低。