Liquid-liquid phase separation of nucleocapsid proteins during SARS-CoV-2 and HIV-1 replication.

Liquid-liquid phase separation of nucleocapsid proteins during SARS-CoV-2 and HIV-1 replication.
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DOI:
10.1016/j.celrep.2022.111968
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发表时间:
2023-01-31
期刊:
影响因子:
8.8
通讯作者:
--
中科院分区:
生物学1区
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--
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逆转录病毒和冠状病毒从动物宿主向人类的飞跃导致了两次持续的大流行,并导致全球数千万人死亡。逆转录病毒和冠状病毒核衣壳蛋白因其在病毒复制中的核心作用而被广泛研究为潜在的药物靶点,其中包括它们与各自的基因组RNA结合以包装成新生病毒粒子的能力。本文综述了这些核衣壳蛋白的基础研究,以及它们通过液-液相分离(LLP)凝聚的内在能力如何有助于病毒复制。还描述了这些凝聚物的治疗靶点和方法学进展,以解决未来关于相分离如何有助于病毒复制的问题。大流行病毒SARS-CoV-2和HIV-1编码的核衣壳蛋白具有内在的紊乱,在病毒复制过程中编程液-液相分离和凝聚。Chau等人。综述最近的文献表明,这对病毒复制至关重要,包括基因表达、组装和基因组包装,以及逃避宿主对感染的先天抗病毒反应。
The leap of retroviruses and coronaviruses from animal hosts to humans has led to two ongoing pandemics and tens of millions of deaths worldwide. Retrovirus and coronavirus nucleocapsid proteins have been studied extensively as potential drug targets due to their central roles in virus replication, among which is their capacity to bind their respective genomic RNAs for packaging into nascent virions. This review focuses on fundamental studies of these nucleocapsid proteins and how their intrinsic abilities to condense through liquid-liquid phase separation (LLPS) contribute to viral replication. Therapeutic targeting of these condensates and methodological advances are also described to address future questions on how phase separation contributes to viral replication. Pandemic viruses SARS-CoV-2 and HIV-1 encode nucleocapsid proteins that possess intrinsic disorder that program liquid-liquid phase separation and condensation during viral replication. Chau et al. review recent literature showing that this is critical for virus replication, including gene expression, assembly, and genome packaging, and evading host anti-viral innate responses to infection.
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