Wang Jingjing, Kliemke Vicky, Zhang Mengyu, Liu Jinxin, Matta Giuliana Leonarda, Wang Qian, Luo Yuhang, Liu GuanQun, Liu Qian
Institute of Parasitology, Faculty of Agricultural and Environmental Sciences, McGill University, Sainte-Anne-de-Bellevue, Quebec, Canada.
Mark Wainberg Center for Viral Diseases, Lady Davis Institute, Montreal, Quebec, Canada.
Sci Adv. 2025 Sep 19;11(38):eadw4609. doi: 10.1126/sciadv.adw4609.
Several enveloped viruses, including paramyxoviruses, assemble and bud from the host plasma membrane (PM). Nipah virus (NiV), a deadly zoonotic paramyxovirus, uses its matrix protein (M) to drive virus assembly and budding through dimerization and PM interaction. We show that NiV-M-mediated virus-like particle (VLP) production depends on its interaction with host F-actin via its carboxyl-terminal domain. We demonstrate that F-actin retains NiV-M assembly sites at the PM by analyzing NiV-M assembly kinetics. Disrupting actin dynamics or NiV-M-actin interaction alters M nanoscale organization and reduces membrane retention, without affecting initial recruitment. We also show that the Arp2/3 complex, an actin-branching factor, promotes VLP production. Inhibiting Arp2/3 reduces NiV-M retention at the PM and impairs protrusion formation while leaving the assembly rate unchanged. These findings suggest that the host F-actin retains NiV assembly sites on the PM and promotes virus budding via Arp2/3-driven actin branching.
包括副粘病毒在内的几种包膜病毒在宿主质膜（PM）上组装并出芽。尼帕病毒（NiV）是一种致命的人畜共患副粘病毒，它利用其基质蛋白（M）通过二聚化和与质膜的相互作用来驱动病毒组装和出芽。我们发现，NiV-M介导的病毒样颗粒（VLP）产生依赖于其通过羧基末端结构域与宿主F-肌动蛋白的相互作用。通过分析NiV-M组装动力学，我们证明F-肌动蛋白将NiV-M组装位点保留在质膜上。破坏肌动蛋白动力学或NiV-M-肌动蛋白相互作用会改变M的纳米级组织并减少膜保留，而不影响初始募集。我们还表明，肌动蛋白分支因子Arp2/3复合物促进VLP产生。抑制Arp2/3会降低NiV-M在质膜上的保留，并损害突起形成，而组装速率不变。这些发现表明，宿主F-肌动蛋白将NiV组装位点保留在质膜上，并通过Arp2/3驱动的肌动蛋白分支促进病毒出芽。
