Department of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, KY 40536-0509, USA.
Virology. 2010 Aug 15;404(1):117-26. doi: 10.1016/j.virol.2010.04.024.
Paramyxovirus fusion (F) proteins promote both virus-cell fusion, required for viral entry, and cell-cell fusion, resulting in syncytia formation. We used the F-actin stabilizing drug, jasplakinolide, and the G-actin sequestrant, latrunculin A, to examine the role of actin dynamics in cell-cell fusion mediated by the parainfluenza virus 5 (PIV5) F protein. Jasplakinolide treatment caused a dose-dependent increase in cell-cell fusion as measured by both syncytia and reporter gene assays, and latrunculin A treatment also resulted in fusion stimulation. Treatment with jasplakinolide or latrunculin A partially rescued a fusion pore opening defect caused by deletion of the PIV5 F protein cytoplasmic tail, but these drugs had no effect on fusion inhibited at earlier stages by either temperature arrest or by a PIV5 heptad repeat peptide. These data suggest that the cortical actin cytoskeleton is an important regulator of fusion pore enlargement, an energetically costly stage of viral fusion protein-mediated membrane merger.
副粘病毒融合（F）蛋白促进病毒进入所需的病毒-细胞融合和导致合胞体形成的细胞-细胞融合。我们使用 F-肌动蛋白稳定药物 jasplakinolide 和 G-肌动蛋白隔离剂 latrunculin A 来研究肌动蛋白动力学在副流感病毒 5（PIV5）F 蛋白介导的细胞-细胞融合中的作用。 jasplakinolide 处理导致细胞-细胞融合的剂量依赖性增加，这可以通过合胞体和报告基因测定来测量，而 latrunculin A 处理也导致融合刺激。用 jasplakinolide 或 latrunculin A 处理部分挽救了由 PIV5 F 蛋白细胞质尾部缺失引起的融合孔开口缺陷，但这些药物对由于温度阻滞或 PIV5 七肽重复肽引起的融合在早期阶段的抑制没有影响。这些数据表明，皮质肌动蛋白细胞骨架是融合孔扩大的重要调节剂，这是病毒融合蛋白介导的膜融合的能量消耗阶段。
