Institute for Integrative Biology of the Cell (I2BC), CEA, CNRS, Univ. Paris-Sud, Université Paris-Saclay, Gif-sur-Yvette cedex, France.
Adv Exp Med Biol. 2019;1215:111-127. doi: 10.1007/978-3-030-14741-9_6.
Replication and assembly of many viruses occur in viral factories which are specialized intracellular compartments formed during viral infection. For rabies virus, those viral factories are called Negri bodies (NBs). NBs are cytoplasmic inclusion bodies in which viral RNAs (mRNAs as well as genomic and antigenomic RNAs) are synthesized. NBs are spherical, they can fuse together, and can reversibly deform when encountering a physical barrier. All these characteristics are similar to those of eukaryotic membrane-less liquid organelles which contribute to the compartmentalization of the cell interior. Indeed, the liquid nature of NBs has been confirmed by FRAP experiments. The co-expression of rabies virus nucleoprotein N and phosphoprotein P is sufficient to induce the formation of cytoplasmic inclusions recapitulating NBs properties. Remarkably, P and N have features similar to those of cellular proteins involved in liquid organelles formation: N is an RNA-binding protein and P contains intrinsically disordered domains. An overview of the literature indicates that formation of liquid viral factories by phase separation is probably common among Mononegavirales. This allows specific recruitment and concentration of viral proteins. Finally, as virus-associated molecular patterns recognized by cellular sensors of RNA virus replication are probably essentially present in the viral factory, there should be a subtle interplay (which remains to be characterized) between those liquid structures and the cellular proteins which trigger the innate immune response.
许多病毒的复制和组装都是在病毒工厂中进行的，这些工厂是在病毒感染过程中形成的专门的细胞内隔室。对于狂犬病病毒，这些病毒工厂被称为 Negri 体（NBs）。NBs 是细胞质内含物，其中合成病毒 RNA（mRNA 以及基因组和抗原基因组 RNA）。NBs 呈球形，它们可以融合在一起，并在遇到物理屏障时可逆地变形。所有这些特征都类似于真核无膜液态细胞器，有助于细胞内部的区室化。事实上，NBs 的液态性质已通过 FRAP 实验得到证实。狂犬病病毒核蛋白 N 和磷蛋白 P 的共表达足以诱导细胞质内含物的形成， recapitulating NBs 的特性。值得注意的是，P 和 N 具有类似于参与液态细胞器形成的细胞蛋白的特征：N 是一种 RNA 结合蛋白，而 P 含有无规卷曲结构域。文献综述表明，通过相分离形成液态病毒工厂可能在 Mononegavirales 中很常见。这允许病毒蛋白的特异性募集和浓缩。最后，由于细胞 RNA 病毒复制传感器识别的病毒相关分子模式很可能基本上存在于病毒工厂中，因此这些液态结构与触发先天免疫反应的细胞蛋白之间应该存在微妙的相互作用（这有待进一步表征）。
