Autor: |
Fu DD; College of Chemistry and Molecular Sciences, Wuhan University, Wuhan 430072, P.R. China., Zhang LJ; College of Chemistry and Molecular Sciences, Wuhan University, Wuhan 430072, P.R. China., Tang B; College of Chemistry and Molecular Sciences, Wuhan University, Wuhan 430072, P.R. China., Du L; College of Chemistry and Molecular Sciences, Wuhan University, Wuhan 430072, P.R. China., Li J; College of Chemistry and Molecular Sciences, Wuhan University, Wuhan 430072, P.R. China., Ao J; College of Chemistry and Molecular Sciences, Wuhan University, Wuhan 430072, P.R. China., Zhang ZL; College of Chemistry and Molecular Sciences, Wuhan University, Wuhan 430072, P.R. China., Wang ZG; State Key Laboratory of Medicinal Chemical Biology, Tianjin Key Laboratory of Biosensing and Molecular Recognition, Frontiers Science Center for New Organic Matter, Research Center for Analytical Sciences, College of Chemistry, Frontiers Science Center for Cell Responses, Nankai University, Tianjin 300071, P. R. China., Liu SL; State Key Laboratory of Medicinal Chemical Biology, Tianjin Key Laboratory of Biosensing and Molecular Recognition, Frontiers Science Center for New Organic Matter, Research Center for Analytical Sciences, College of Chemistry, Frontiers Science Center for Cell Responses, Nankai University, Tianjin 300071, P. R. China., Pang DW; College of Chemistry and Molecular Sciences, Wuhan University, Wuhan 430072, P.R. China.; State Key Laboratory of Medicinal Chemical Biology, Tianjin Key Laboratory of Biosensing and Molecular Recognition, Frontiers Science Center for New Organic Matter, Research Center for Analytical Sciences, College of Chemistry, Frontiers Science Center for Cell Responses, Nankai University, Tianjin 300071, P. R. China. |
Abstrakt: |
After entering host cells by endocytosis, influenza A virus (IAV) is transported along microfilaments and then transported by dynein along microtubules (MTs) to the perinuclear region for genome release. Understanding the mechanisms of dynein-driven transport is significant for a comprehensive understanding of IAV infection. In this work, the roles of dynactin in dynein-driven transport of IAV were quantitatively dissected in situ using quantum dot-based single-virus tracking. It was revealed that dynactin was essential for dynein to transport IAV toward the nucleus. After virus entry, virus-carrying vesicles bound to dynein and dynactin before being delivered to MTs. The attachment of dynein to the vesicles was dependent on dynactin and its subunits, p150 Glued and Arp1. Once viruses reached MTs, dynactin-assisted dynein initiates retrograde transport of IAV. Importantly, the retrograde transport of viruses could be initiated at both plus ends (32%) and other regions on MTs (68%). Subsequently, dynactin accompanied and assisted dynein to persistently transport the virus along MTs in the retrograde direction. This study revealed the dynactin-dependent dynein-driven transport process of IAV, enhancing our understanding of IAV infection and providing important insights into the cell's endocytic transport mechanism. |