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FAM111B的E2F3依赖激活限制了老鼠细胞巨乳病毒在灵长类细胞中的复制

Eleonore Ostermann¹, Laura-Marie Luoto¹, Michaela Clausen¹

¹Leibniz Institute of Virology (LIV), Hamburg, Germany.

Journal of virology

|November 4, 2024

概括

由于FAM111B,一种灵长类动物特异性蛋白质,小鼠细胞巨乳病毒 (MCMV) 不能在人类细胞中复制. FAM111B抑制了MCMV复制,解释了这种病毒对宿主物种的限制.

科学领域:

病毒学病毒学
免疫学免疫学免疫学
遗传学遗传学是一种遗传学.

背景情况:

细胞巨乳病毒 (CMV) 具有严格的物种特异性,限制其复制到特定的宿主细胞.
在CMV中这种宿主范围的限制背后的分子机制在很大程度上是未知的.
以前的研究表明,适应性突变使小鼠CMV (MCMV) 在人体细胞中复制.

研究的目的:

阐明负责限制非宿主物种MCMV复制的细胞因素.
调查E2F转录因子及其下游目标在MCMV主机限制中的作用.
为了识别和描述MCMV的新宿主限制因素.

主要方法:

转录组分析以确定E2F3诱导的基因.
使用shRNA进行基因淘汰,使用CRISPR/Cas9.9进行基因淘汰.
免疫光检测以确定FAM111B在受感染细胞中的定位.

主要成果:

确定E2F3激活是MCMV无法在人体细胞中复制的一个关键因素.
发现FAM111B是一种E2F3诱导的血清蛋白酶,可以抑制人类和 rhesus细胞中的MCMV复制.
FAM111B定位在感染细胞核中的病毒复制区.

结论:

FAM111B作为一种限制宿主因子,限制了灵长类动物细胞中的MCMV复制.
在动物中缺乏FAM111B解释了为什么MCMV没有进化以克服这种特定的限制.
FAM111B代表了MCMV跨物种传播的重大障碍,并提供了对病毒宿主范围的见解.

关键词:

E2F3 E2F3 E2F3 E2F3 E2F3 E2F3 E2F3 E2F3 E2F3 这就是FAM111B.细胞巨型病毒 (cytomegalovirus) 是一种病毒.主机范围的主机范围.限制因子的限制因子种类的特异性,物种的特异性.

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