title: The dynactin complex enhances the speed of microtubule-dependent motions of adenovirus both towards and away from the nucleus.
abstract: Unlike transport vesicles or organelles, human adenovirus (HAdV) directly binds to the microtubule minus end-directed motor dynein for transport to the nucleus. The dynein cofactor dynactin enhances nuclear transport of HAdV and boosts infection. To determine if dynactin has a specific role in cytoplasmic trafficking of incoming HAdV on microtubules, we used live cell spinning disc confocal microscopy at 25 Hz acquisition frequency and automated tracking of single virus particles at 20-50 nm spatial resolution. Computational dissection by machine-learning algorithms extracted specific motion patterns of viral trajectories. We found that unperturbed cells supported two kinds of microtubule-dependent motions, directed motions (DM) and fast drifts (FD). DM had speeds of 0.2 to 2 μm/s and run lengths of 0.4 up to 7 μm, while FD were slower and less extensive at 0.02 to 0.4 μm/s and 0.05 to 2.5 μm. Dynactin interference by overexpression of p50/dynamitin or a coiled-coil domain of p150/Glued reduced the speeds and amounts of both center- and periphery-directed DM but not FD, and inhibited infection. These results indicate that dynactin enhances adenovirus infection by increasing the speed and efficiency of dynein-mediated virus motion to the nucleus, and, surprisingly, also supports a hereto unknown motor activity for virus transport to the cell periphery.
authors: Institute of Molecular Life Sciences, University of Zurich, Zurich 8057, Switzerland.|Molecular Life Sciences Graduate School, ETH and University of Zurich, Zurich 8057, Switzerland.
authors: Martin F
authors: MF
authors: Engelke
authors: Institute of Molecular Life Sciences, University of Zurich, Zurich 8057, Switzerland.
authors: Christoph J
authors: CJ
authors: Burckhardt
authors: Institute of Molecular Life Sciences, University of Zurich, Zurich 8057, Switzerland.|Molecular Life Sciences Graduate School, ETH and University of Zurich, Zurich 8057, Switzerland.
authors: Matthias K
authors: MK
authors: Morf
authors: Institute of Molecular Life Sciences, University of Zurich, Zurich 8057, Switzerland.
authors: Urs F
authors: UF
authors: Greber
mesh_terms: D000258:Adenovirus Infections, Human / Q000378:metabolism / Q000821:virology*; D000260:Adenoviruses, Human / Q000502:physiology*; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism / Q000821:virology*; D000072159:Dynactin Complex; D004398:Dyneins / Q000378:metabolism; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism / Q000821:virology*
chemical_list: C000606360:DCTN1 protein, human; C000606361:DCTN2 protein, human; D000072159:Dynactin Complex; D008869:Microtubule-Associated Proteins; D004398:Dyneins