Abstract
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.
Highlights
Viruses affect all forms of life, from bacteria to humans
Upon virion endocytosis and endosomal escape where the membrane lytic viral protein VI is fully exposed from the virion, the partially dismantled capsids are transported to the nuclear envelope in a microtubule-dependent manner [63,179,180]
The knowledge emerges from analyses of virion trajectories by computational methods, and in silico simulation experiments
Summary
Viruses affect all forms of life, from bacteria to humans. They are a product of co-evolution with their hosts, and cause disease, or assist in gene and anti-microbial therapies [1,2,3,4]. DNA virus, which starts its uncoating program by shedding the fiber proteins at the cell surface, and continues releasing minor virion components in a stepwise manner [25,26,27,28] For some viruses, such as influenza virus (IV) and AdV, complete genome uncoating requires the acto-myosin and microtubule cytoskeleton [11,29,30]. Other viruses, such as human immunodeficiency virus (HIV) or poxviruses transcribe their genome while located in the cytosol and at least partly wrapped by their capsid [31,32,33,34]. A list of fluorescent virus particles from both non-enveloped and enveloped families, and the methods by which the virions were prepared is presented in
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