Getah virus capsid protein undergoes co-condensation with viral genomic RNA to facilitate virion assembly

文献类型： 外文期刊

第一作者： Sun, Zhenzhao

作者： Sun, Zhenzhao;Wang, Wenmeng;Li, Dangdang;Sui, Guangchao;Wang, Ming;Wang, Jingfei;Wang, Ming;Wang, Jingfei

作者机构：

关键词： Getah virus; Capsid protein; Genome RNA; Liquid -liquid phase separation; Virion assembly

期刊名称：INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES （ 影响因子：8.2； 五年影响因子：7.8 ）

ISSN： 0141-8130

年卷期： 2024 年 265 卷

页码：

收录情况： SCI

摘要： Getah virus (GETV) belongs to the Alphavirus genus in the Togaviridae family and is a zoonotic arbovirus causing disease in both humans and animals. The capsid protein (CP) of GETV regulates the viral core assembly, but the mechanism underlying this process is poorly understood. In this study, we demonstrate that CP undergoes liquidliquid phase separation (LLPS) with the GETV genome RNA (gRNA) in vitro and forms cytoplasmic puncta in cells. Two regions of GETV gRNA (nucleotides 1 - 4000 and 5000-8000) enhance CP droplet formation in vitro and the lysine -rich Link region of CP is essential for its phase separation. CP(K/R) mutant with all lysines in the Link region replaced by arginines exhibits improved LLPS versus wild type (WT) CP, but CP(K/E) mutant with lysines substituted by glutamic acids virtually loses condensation ability. Consistently, recombinant virus mutant with CP(K/R) possesses significantly higher gRNA binding affinity, virion assembly efficiency and infectivity than the virus with WT-CP. Overall, our findings provide new insights into the understanding of GETV assembly and development of new antiviral drugs against alphaviruses.

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