Borna disease virus phosphoprotein triggers the organization of viral inclusion bodies by liquid-liquid phase separation
Borna disease virus phosphoprotein triggers the organization of viral inclusion bodies by liquid-liquid phase separation
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DOI：
10.1016/j.ijbiomac.2021.09.153
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发表时间：
2021-10-05
影响因子：
8.2
通讯作者：
Horie, Masayuki
中科院分区：
文献类型：
--
作者：
Hirai, Yuya;Tomonaga, Keizo;Horie, Masayuki
包涵体（IBs）是单链病毒（Mononegavirales）中非分节负链RNA病毒组织的特征性生物分子凝聚体。尽管最近的研究揭示了由细胞质单核病毒形成的肠易激综合征的特征，但博纳病病毒1 （BoDV-1）的特征仍然难以捉摸，BoDV-1是一种在细胞核中形成肠易激综合征并建立持续感染的独特单核病毒。在这里，我们从液-液相分离（LLPS）的角度描述了BoDV-1的IBs。体外实验中，BoDV-1磷酸化蛋白(P)单独诱导LLPS，核蛋白(N)被掺入到P液滴中。相反，细胞中形成ib样结构需要N和P的共同表达。此外，当BoDV-1 P与RNA结合时，过量的RNA会溶解体外N和P形成的液滴。值得注意的是，BoDV-1 P内在无序的n端区域对于驱动LLPS和与RNA结合至关重要，这表明这两种能力可能相互竞争。这些特征在单核病毒中是独一无二的，因此这项研究将有助于更深入地了解llps驱动的组织和rna介导的生物分子凝聚物的调控。
Inclusion bodies (IBs) are characteristic biomolecular condensates organized by the non-segmented negative strand RNA viruses belonging to the order Mononegavirales. Although recent studies have revealed the characteristics of IBs formed by cytoplasmic mononegaviruses, that of Borna disease virus 1 (BoDV-1), a unique mononegavirus that forms IBs in the cell nucleus and establishes persistent infection remains elusive. Here, we characterize the IBs of BoDV-1 in terms of liquid-liquid phase separation (LLPS). The BoDV-1 phosphoprotein (P) alone induces LLPS and the nucleoprotein (N) is incorporated into the P droplets in vitro. In contrast, co expression of N and P is required for the formation of IB-like structure in cells. Furthermore, while BoDV-1 P binds to RNA, an excess amount of RNA dissolves the liquid droplets formed by N and P in vitro. Notably, the intrinsically disordered N-terminal region of BoDV-1 P is essential to drive LLPS and to bind to RNA, suggesting that both abilities could compete with one another. These features are unique among mononegaviruses, and thus this study will contribute to a deeper understanding of LLPS-driven organization and RNA-mediated regulation of biomolecular condensates.