A “Driver Switchover” Mechanism of Influenza Virus Transport from Microfilaments to Microtubules

Abstract

When infecting host cells, influenza virus must move on microfilaments (MFs) at the cell periphery and then move along microtubules (MTs) through the cytosol to reach the perinuclear region for genome release. But how viruses switch from the actin roadway to the microtubule highway remains obscure. To settle this issue, we systematically dissected the role of related motor proteins in the transport of influenza virus between cytoskeletal filaments in situ and in real-time using quantum dot (QD)-based single-virus tracking (SVT) and multicolor imaging. We found that the switch between MF- and MT-based retrograde motor proteins, myosin VI (myoVI) and dynein, was responsible for the seamless transport of viruses from MFs to MTs during their infection. After virus entry by endocytosis, both the two types of motor proteins are attached to virus-carrying vesicles. MyoVI drives the viruses on MFs with dynein on the virus-carrying vesicle hitchhiking. After role exchanges at actin-microtubule intersections, dynein drives the virus along MTs toward the perinuclear region with myoVI remaining on the vesicle moving together. Such a "driver switchover" mechanism has answered the long-pending question of how viruses switch from MFs to MTs for their infection. It will also facilitate in-depth understanding of endocytosis.

Microtubules in Influenza Virus Entry and Egress

“…While some viruses, including herpes, polyoma, adeno, and adeno-associated viruses, are able to directly interact with microtubular motor proteins for transport [54][55][56][57], others, including IAV, rely on endocytic vesicles for interaction with and traffic along microtubules [58]. Within the cellular periphery, endosomes and their cargo interact with actin filaments [59,60], which, together with their associated myosin motors, facilitate the short, back and forth motion of EEs. As endosomes move towards the cellular interior, retrograde transport becomes dependent upon microtubules and their associated dynein motors [61][62][63].…”

“…The depolymerisation of the microtubular network induces the dispersal of mature endosomes throughout the cytoplasm [66]. Intact microtubules promote IAV entry into cells [58,60,[67][68][69][70][71]. Real-time fluorescent microscopy studies of individual influenza viruses, along with quantum-dot based viral tracking techniques, have provided evidence that endosome-contained IAVs utilise classical endocytic pathways and microtubules during transit through the cytoplasm (Figure 1) [58,60,72].…”

“…Intact microtubules promote IAV entry into cells [58,60,[67][68][69][70][71]. Real-time fluorescent microscopy studies of individual influenza viruses, along with quantum-dot based viral tracking techniques, have provided evidence that endosome-contained IAVs utilise classical endocytic pathways and microtubules during transit through the cytoplasm (Figure 1) [58,60,72]. Specifically, IAVs induce the formation of clathrin coated pits (CCPs) for uptake into endocytic vesicles, and also use caveolin-independent endocytosis and pinocytic uptake mechanisms [69,73].…”

Lipid-specific labeling of enveloped viruses with quantum dots for single-virus tracking

“…The excellent optical properties make QDs unparalleled in single-molecule/virus tracking. Single molecules/viruses illuminated with QDs can be rapidly and continuously tracked for a long time [5, 6], and their interactions with multiple other molecules can be monitored simultaneously [7-9], providing more detailed information to dissect cellular events than those labeled by other fluorophores. Thanks to these advantages, QDs have been widely used to label proteins for single-molecule tracking studies [10-17].…”

Study on the solitary wave solutions of the ionic currents on microtubules equation by using the modified Khater method

“…It is not only just that but also supply platforms for intracellular transport. Microtubules are implicated in miscellaneous of cellular processes and also inclusive the movement of secretory vesicles, organelles [1][2][3][4][5][6][7][8][9][10]. Li Marc Kirschner and Tim Mitchison suggested in (1986s) that, the microtubules can employ its dynamic characteristics of growth and contraction at their plus ends to probe the 3-D space of the cell.…”