Quantitatively\nDissecting Triple Roles of Dynactin\nin Dynein-Driven Transport of Influenza Virus by Quantum Dot-Based\nSingle-Virus Tracking

After\nentering host cells by endocytosis, influenza A virus (IAV)\nis transported along microfilaments and then transported by dynein\nalong microtubules (MTs) to the perinuclear region for genome release.\nUnderstanding the mechanisms of dynein-driven transport is significant\nfor a comprehensive understanding of IAV infection. In this work,\nthe roles of dynactin in dynein-driven transport of IAV were quantitatively\ndissected <i>in situ</i> using quantum dot-based single-virus\ntracking. It was revealed that dynactin was essential for dynein to\ntransport IAV toward the nucleus. After virus entry, virus-carrying\nvesicles bound to dynein and dynactin before being delivered to MTs.\nThe attachment of dynein to the vesicles was dependent on dynactin\nand its subunits, p150<sup>Glued</sup> and Arp1. Once viruses reached\nMTs, dynactin-assisted dynein initiates retrograde transport of IAV.\nImportantly, the retrograde transport of viruses could be initiated\nat both plus ends (32%) and other regions on MTs (68%). Subsequently,\ndynactin accompanied and assisted dynein to persistently transport\nthe virus along MTs in the retrograde direction. This study revealed\nthe dynactin-dependent dynein-driven transport process of IAV, enhancing\nour understanding of IAV infection and providing important insights\ninto the cell’s endocytic transport mechanism.