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Viruses. 2018 Mar 31;10(4). pii: E166. doi: 10.3390/v10040166.

Imaging, Tracking and Computational Analyses of Virus Entry and Egress with the Cytoskeleton.

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Division of Virology, Institute of Medical Science, the University of Tokyo, Tokyo 108-8639, Japan.
Lyda Hill Department of Bioinformatics, UT Southwestern Medical Center, Dallas, TX 75390, USA.
MRC Laboratory for Molecular Cell Biology, University College London, London WC1E 6BT, UK.
Department of Molecular Life Sciences, University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland.


Viruses have a dual nature: particles are “passive substances” lacking chemical energy transformation, whereas infected cells are “active substances” turning-over energy. How passive viral substances convert to active substances, comprising viral replication and assembly compartments has been of intense interest to virologists, cell and molecular biologists and immunologists. Infection starts with virus entry into a susceptible cell and delivers the viral genome to the replication site. This is a multi-step process, and involves the cytoskeleton and associated motor proteins. Likewise, the egress of progeny virus particles from the replication site to the extracellular space is enhanced by the cytoskeleton and associated motor proteins. This overcomes the limitation of thermal diffusion, and transports virions and virion components, often in association with cellular organelles. This review explores how the analysis of viral trajectories informs about mechanisms of infection. We discuss the methodology enabling researchers to visualize single virions in cells by fluorescence imaging and tracking. Virus visualization and tracking are increasingly enhanced by computational analyses of virus trajectories as well as in silico modeling. Combined approaches reveal previously unrecognized features of virus-infected cells. Using select examples of complementary methodology, we highlight the role of actin filaments and microtubules, and their associated motors in virus infections. In-depth studies of single virion dynamics at high temporal and spatial resolutions thereby provide deep insight into virus infection processes, and are a basis for uncovering underlying mechanisms of how cells function.


DNA virus; Modeling; RNA virus; actin; adeno-associated virus AAV; adenovirus; baculovirus; cell biology; click chemistry; computing; cytoskeleton; dynein; electron microscopy; endocytosis; enveloped virus; fluorescence microscopy; fluorescent virions; gene expression; gene therapy; hepatitis B virus; herpes simplex virus; herpesvirus; human immunodeficiency virus HIV; immunofluorescence microscopy; infection; influenza virus; innate immunity; internalization; intracellular transport; kinesin; machine learning; membrane traffic; microscopy; microtubule; myosin; nonenveloped virus; nuclear pore complex; parvovirus; quantitative microscopy; receptor; simian virus 40; simulation; single particle tracking; tracking; trafficking; trajectory segmentation; virion uncoating; virus entry; virus infection mechanisms

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