Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA.
Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA.
Curr Biol. 2018 Jul 9;28(13):2153-2159.e4. doi: 10.1016/j.cub.2018.05.027. Epub 2018 Jun 28.
Viruses that replicate in the host cell nucleus face challenges in usurping cellular pathways to enable passage through the nuclear envelope [1]. Baculoviruses are enveloped, double-stranded DNA viruses that infect lepidopteran insects and are tools for protein expression, cell transduction, and pest management [2-4]. 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 [5]. During early infection, actin-based motility in the cytoplasm speeds AcMNPV transit to the nucleus and passage through nuclear pores, enabling nuclear ingress [6, 7]. During late infection, AcMNPV assembles F-actin within the nucleus [8], which is essential for virus production [9, 10]. However, the function of nuclear F-actin is poorly understood [11], 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.
在宿主细胞核内复制的病毒在篡夺细胞途径以穿过核膜时面临挑战[1]。杆状病毒是包膜的双链 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[2-4]。模式种加利福尼亚棉铃虫多角体病毒（AcMNPV）与其他病原体一样，具有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[5]。在早期感染中，细胞质中的肌动蛋白运动加速 AcMNPV 向核内的转运和核孔的通过，从而实现核内进入[6,7]。在晚期感染中，AcMNPV 在核内组装 F-肌动蛋白[8]，这对病毒的产生至关重要[9,10]。然而，核 F-肌动蛋白的功能尚未得到很好的理解[11]，其在 AcMNPV 感染中的机制作用尚不清楚。我们表明 AcMNPV 可在核内动员肌动蛋白以促进出芽。AcMNPV 核衣壳在核内表现出基于肌动蛋白的运动，由病毒蛋白 P78/83 和宿主 Arp2/3 复合物介导。病毒运动驱动向核周质的转移，这是病毒进入核膜突起所必需的。此外，肌动蛋白聚合对于病毒在出芽过程中断裂核膜完整性是必需的。在细胞质中，病毒利用肌动蛋白运动到达质膜以进行出芽。我们的结果表明，病原体可以利用肌动蛋白聚合来破坏核膜。利用肌动蛋白破坏核膜完整性可能反映了病毒对核肌动蛋白正常功能的篡夺，包括核膜完整性、稳定性和重塑。
