Advanced Molecular Virology and Retroviral Dynamics Group, Department of Virology, Pasteur Institute, Paris, France.
BioSPC Doctoral School, Universitè de Paris, Paris, France.
J Mol Cell Biol. 2021 Aug 4;13(4):259-268. doi: 10.1093/jmcb/mjab020.
Viruses hijack host functions to invade their target cells and spread to new cells. Specifically, viruses learned to usurp liquid‒liquid phase separation (LLPS), a newly exploited mechanism, used by the cell to concentrate enzymes to accelerate and confine a wide variety of cellular processes. LLPS gives rise to actual membraneless organelles (MLOs), which do not only increase reaction rates but also act as a filter to select molecules to be retained or to be excluded from the liquid droplet. This is exactly what seems to happen with the condensation of SARS-CoV-2 nucleocapsid protein to favor the packaging of intact viral genomes, excluding viral subgenomic or host cellular RNAs. Another older pandemic virus, HIV-1, also takes advantage of LLPS in the host cell during the viral cycle. Recent discoveries highlighted that HIV-1 RNA genome condensates in nuclear MLOs accompanied by specific host and viral proteins, breaking the dogma of retroviruses that limited viral synthesis exclusively to the cytoplasmic compartment. Intriguing fundamental properties of viral/host LLPS remain still unclear. Future studies will contribute to deeply understanding the role of pathogen-induced MLOs in the epidemic invasion of pandemic viruses.
病毒劫持宿主功能以入侵其靶细胞并传播到新细胞。具体来说，病毒学会了利用液-液相分离（LLPS），这是一种新开发的机制，被细胞用来浓缩酶以加速和限制各种细胞过程。LLPS 产生了实际的无膜细胞器（MLOs），这不仅提高了反应速率，而且还起到了筛选分子的作用，将分子保留在液滴中或排除在液滴之外。这正是 SARS-CoV-2 核衣壳蛋白凝聚有利于完整病毒基因组包装的情况，排除了病毒亚基因组或宿主细胞 RNA。另一种较旧的大流行病毒 HIV-1 也在病毒周期中利用宿主细胞中的 LLPS。最近的发现强调，HIV-1 RNA 基因组在核 MLO 中凝聚，伴随着特定的宿主和病毒蛋白，打破了逆转录病毒的教条，即病毒合成仅限于细胞质区室。病毒/宿主 LLPS 的有趣基本性质仍然不清楚。未来的研究将有助于深入了解病原体诱导的 MLO 在大流行病毒流行入侵中的作用。
