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PLoS Biol. 2014 Jan;12(1):e1001765. doi: 10.1371/journal.pbio.1001765. Epub 2014 Jan 14.

Electron tomography and simulation of baculovirus actin comet tails support a tethered filament model of pathogen propulsion.

Author information

1
Institute of Molecular Biotechnology, Austrian Academy of Sciences, Vienna, Austria.
2
RICAM, Austrian Academy of Sciences, Vienna, Austria ; Faculty of Mathematics, University of Vienna, Austria.
3
Nagoya University, Graduate School of Sciences, Structural Biology Research Center and Division of Biological Sciences, Nagoya, Japan ; Nagoya University JST PRESTO, 4-1-8 Honcho Kawaguchi, Saitama, Japan.
4
Laboratoire d'Enzymologie et Biochimie Structurales, Centre National de la Recherche Scientifique, Gif-sur-Yvette, France.
5
Nagoya University, Graduate School of Sciences, Structural Biology Research Center and Division of Biological Sciences, Nagoya, Japan.
6
Department of Molecular and Cell Biology, University of California, Berkeley, California, United States of America.
7
Campus Science Support Facilities GmbH, Vienna, Austria.

Abstract

Several pathogens induce propulsive actin comet tails in cells they invade to disseminate their infection. They achieve this by recruiting factors for actin nucleation, the Arp2/3 complex, and polymerization regulators from the host cytoplasm. Owing to limited information on the structural organization of actin comets and in particular the spatial arrangement of filaments engaged in propulsion, the underlying mechanism of pathogen movement is currently speculative and controversial. Using electron tomography we have resolved the three-dimensional architecture of actin comet tails propelling baculovirus, the smallest pathogen yet known to hijack the actin motile machinery. Comet tail geometry was also mimicked in mixtures of virus capsids with purified actin and a minimal inventory of actin regulators. We demonstrate that propulsion is based on the assembly of a fishbone-like array of actin filaments organized in subsets linked by branch junctions, with an average of four filaments pushing the virus at any one time. Using an energy-minimizing function we have simulated the structure of actin comet tails as well as the tracks adopted by baculovirus in infected cells in vivo. The results from the simulations rule out gel squeezing models of propulsion and support those in which actin filaments are continuously tethered during branch nucleation and polymerization. Since Listeria monocytogenes, Shigella flexneri, and Vaccinia virus among other pathogens use the same common toolbox of components as baculovirus to move, we suggest they share the same principles of actin organization and mode of propulsion.

PMID:
24453943
PMCID:
PMC3891563
DOI:
10.1371/journal.pbio.1001765
[Indexed for MEDLINE]
Free PMC Article

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