基于肌动蛋白和微管(MT)的运输系统对于细胞内运输至关重要。在甲型流感病毒(IAV)感染期间,MTs为病毒向细胞核贩运提供了很长的踪迹。然而,肌动蛋白细胞骨架在IAV进入,特别是转运过程中的作用仍然不明确。这里,通过使用基于量子点的单病毒跟踪,结果表明,肌动蛋白细胞骨架对于通过网格蛋白介导的内吞作用(CME)进入病毒至关重要。通过CME进入后,病毒通过三种不同的途径到达MTs:病毒(1)由肌球蛋白VI驱动,沿着肌动蛋白丝移动,到达MTs(AF);(2)由Arp2/3依赖性机制组装的肌动蛋白尾推动,到达MTs(AT);(3)直接到达MTs,而没有发生与肌动蛋白相关的运动(NA).因此,NA途径是病毒到达MTs的主要途径,也是最快的途径。只有当大量病毒进入细胞时,AT途径才被激活。通过AF和AT途径运输的病毒具有相似的移动速度,持续时间,和流离失所。这项研究全面可视化了肌动蛋白细胞骨架在IAV进入和运输中的作用,揭示IAV进入后到达MTs的不同途径。该结果对于全球了解IAV感染和细胞内吞转运途径具有重要意义。
Actin- and microtubule (MT)-based transport systems are essential for intracellular transport. During influenza A virus (IAV) infection, MTs provide long tracks for virus trafficking toward the nucleus. However, the role of the actin cytoskeleton in IAV entry and especially the transit process is still ambiguous. Here, by using quantum dot-based single-virus tracking, it was revealed that the actin cytoskeleton was crucial for the virus entry via clathrin-mediated endocytosis (CME). After entry via CME, the virus reached MTs through three different pathways: the virus (1) was driven by myosin VI to move along actin filaments to reach MTs (AF); (2) was propelled by actin tails assembled by an Arp2/3-dependent mechanism to reach MTs (AT); and (3) directly reached MTs without experiencing actin-related movement (NA). Therefore, the NA pathway was the main one and the fastest for the virus to reach MTs. The AT pathway was activated only when plenty of viruses entered the cell. The viruses transported by the AF and AT pathways shared similar moving velocities, durations, and displacements. This study comprehensively visualized the role of the actin cytoskeleton in IAV entry and transport, revealing different pathways for IAV to reach MTs after entry. The results are of great significance for globally understanding IAV infection and the cellular endocytic transport pathway.