Cell Biology of Viral Infection Lab, Instituto Gulbenkian de Ciência, 2780-156, Oeiras, Portugal.
Electron Microscopy Facility, Instituto Gulbenkian de Ciência, 2780-156, Oeiras, Portugal.
Nat Commun. 2019 Apr 9;10(1):1629. doi: 10.1038/s41467-019-09549-4.
Influenza A virus has an eight-partite RNA genome that during viral assembly forms a complex containing one copy of each RNA. Genome assembly is a selective process driven by RNA-RNA interactions and is hypothesized to lead to discrete punctate structures scattered through the cytosol. Here, we show that contrary to the accepted view, formation of these structures precedes RNA-RNA interactions among distinct viral ribonucleoproteins (vRNPs), as they assemble in cells expressing only one vRNP type. We demonstrate that these viral inclusions display characteristics of liquid organelles, segregating from the cytosol without a delimitating membrane, dynamically exchanging material and adapting fast to environmental changes. We provide evidence that viral inclusions develop close to endoplasmic reticulum (ER) exit sites, depend on continuous ER-Golgi vesicular cycling and do not promote escape to interferon response. We propose that viral inclusions segregate vRNPs from the cytosol and facilitate selected RNA-RNA interactions in a liquid environment.
甲型流感病毒具有一个八部分的 RNA 基因组，在病毒组装过程中形成一个包含每种 RNA 一份拷贝的复合物。基因组组装是一个由 RNA-RNA 相互作用驱动的选择性过程，据推测会导致离散的点状结构散布在细胞质中。在这里，我们表明与公认的观点相反，这些结构的形成先于不同的病毒核糖核蛋白（vRNP）之间的 RNA-RNA 相互作用，因为它们在仅表达一种 vRNP 类型的细胞中组装。我们证明这些病毒包含物表现出液体细胞器的特征，在没有限定膜的情况下从细胞质中分离出来，动态地交换物质并快速适应环境变化。我们提供的证据表明，病毒包含物在靠近内质网（ER）出口部位形成，依赖于 ER-Golgi 囊泡循环的连续性，并且不会促进干扰素反应的逃逸。我们提出病毒包含物将 vRNP 从细胞质中分离出来，并在液体环境中促进选定的 RNA-RNA 相互作用。
