Baculovirus Actin-Based Motility Drives Nuclear Envelope Disruption and Nuclear Egress.

Baculovirus Actin-Based Motility Drives Nuclear Envelope Disruption and Nuclear Egress.
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DOI:
10.1016/j.cub.2018.05.027
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发表时间:
2018-07-09
期刊:
Current biology : CB
影响因子:
--
通讯作者:
Welch MD
Welch MD
中科院分区:
其他
文献类型:
--
作者:
Ohkawa T;Welch MD

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在宿主细胞核中复制的病毒在篡夺细胞途径以使其能够通过核膜方面面临挑战。杆状病毒是一种有包膜的双链DNA病毒,感染鳞翅目昆虫,是蛋白质表达、细胞转导和害虫管理的工具。模式种苜蓿银纹夜蛾M核型多角体病毒(AcMNPV)与其他病原体共享将宿主肌动蛋白单体(G-肌动蛋白)组装成肌动蛋白丝(F-肌动蛋白)以驱动运动的能力。在早期感染期间,细胞质中基于肌动蛋白的运动性加速AcMNPV转运到细胞核并通过核孔,从而使细胞核进入。在晚期感染过程中,AcMNPV在细胞核内组装F-肌动蛋白,这对病毒的产生至关重要。然而,核F-肌动蛋白的功能知之甚少,其在AcMNPV感染的机制作用是未知的。我们发现,AcMNPV调动细胞核内的肌动蛋白,以促进出口。AcMNPV核衣壳表现出核内肌动蛋白为基础的运动,介导的病毒蛋白P78/83和主机Arp 2/3复合物。病毒运动性驱动转运到核外围,并且是病毒进入核膜突起所需的。此外,肌动蛋白聚合是必要的病毒破坏核膜的完整性在出口。在细胞质中,病毒利用肌动蛋白为基础的运动到达质膜,使出芽。我们的研究结果表明,病原体可以利用肌动蛋白聚合破坏核膜。利用肌动蛋白破坏核膜可能反映了病毒对核肌动蛋白在核膜完整性、稳定性和重塑中的正常功能的占用。
Viruses that replicate in the host cell nucleus face challenges in usurping cellular pathways to enable passage through the nuclear envelope. Baculoviruses are enveloped, double-stranded DNA viruses that infect lepidopteran insects and are tools for protein expression, cell transduction and pest management. The type species Autographa californica M nucleopolyhedrovirus (AcMNPV) shares with other pathogens an ability to assemble host actin monomers (G-actin) into actin filaments (F-actin) to drive motility. During early infection, actin-based motility in the cytoplasm speeds AcMNPV transit to the nucleus and passage through nuclear pores, enabling nuclear ingress. During late infection, AcMNPV assembles F-actin within the nucleus, which is essential for virus production. However, the function of nuclear F-actin is poorly understood, and its mechanistic role in AcMNPV infection was unknown. We show that AcMNPV mobilizes actin within the nucleus to promote egress. AcMNPV nucleocapsids exhibit intranuclear actin-based motility, mediated by the viral protein P78/83 and the host Arp2/3 complex. Viral motility drives transit to the nuclear periphery and is required for viruses to enter protrusions of the nuclear envelope. Moreover, actin polymerization is necessary for viral disruption of nuclear envelope integrity during egress. In the cytoplasm, viruses use actin-based motility to reach the plasma membrane to enable budding. Our results demonstrate that pathogens can harness actin polymerization to disrupt the nuclear envelope. Employing actin for nuclear envelope disruption may reflect viral appropriation of normal functions of nuclear actin in nuclear envelope integrity, stability, and remodeling.
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