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Virus movements on the plasma membrane support infection and transmission between cells.

ABSTRACT: How viruses are transmitted across the mucosal epithelia of the respiratory, digestive, or excretory tracts, and how they spread from cell to cell and cause systemic infections, is incompletely understood. Recent advances from single virus tracking experiments have revealed conserved patterns of virus movements on the plasma membrane, including diffusive motions, drifting motions depending on retrograde flow of actin filaments or actin tail formation by polymerization, and confinement to submicrometer areas. Here, we discuss how viruses take advantage of cellular mechanisms that normally drive the movements of proteins and lipids on the cell surface. A concept emerges where short periods of fast diffusive motions allow viruses to rapidly move over several micrometers. Coupling to actin flow supports directional transport of virus particles during entry and cell-cell transmission, and local confinement coincides with either nonproductive stalling or infectious endocytic uptake. These conserved features of virus-host interactions upstream of infectious entry offer new perspectives for anti-viral interference.

SUBMITTER: Burckhardt CJ

PROVIDER: S-EPMC2777510 | biostudies-other | 2009 Nov

REPOSITORIES: biostudies-other

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Project description:Viruses spread between cells, tissues, and organisms by cell-free and cell-cell mechanisms, depending on the cell type, the nature of the virus, or the phase of the infection cycle. The mode of viral transmission has a large impact on disease development, the outcome of antiviral therapies or the efficacy of gene therapy protocols. The transmission mode of viruses can be addressed in tissue culture systems using live-cell imaging. Yet even in relatively simple cell cultures, the mechanisms of viral transmission are difficult to distinguish. Here we present a cross-platform software framework called "Infectio," which is capable of simulating transmission phenotypes in tissue culture of virtually any virus. Infectio can estimate interdependent biological parameters, for example for vaccinia virus infection, and differentiate between cell-cell and cell-free virus spreading. Infectio assists in elucidating virus transmission mechanisms, a feature useful for designing strategies of perturbing or enhancing viral transmission. The complexity of the Infectio software is low compared to that of other software commonly used to quantitate features of cell biological images, which yields stable and relatively error-free output from Infectio. The software is open source (GPLv3 license), and operates on the major platforms (Windows, Mac, and Linux). The complete source code can be downloaded from http://infectio.github.io/index.html. IMPORTANCE Infectio presents a generalized platform to analyze virus infection spread between cells. It allows the simulation of plaque phenotypes from image-based assays. Viral plaques are the result of virus spreading from primary infected cells to neighboring cells. This is a complex process and involves neighborhood effects at cell-cell contact sites or fluid dynamics in the extracellular medium. Infectio differentiates between two major modes of virus transmission between cells, allowing in silico testing of hypotheses about spreading mechanisms of any virus which can be grown in cell cultures, based on experimentally measured parameters, such as infection intensity or cell killing. The results of these tests can be compared with experimental data and allow interpretations with regard to biophysical mechanisms. Infectio also facilitates characterizations of the mode of action of therapeutic agents, such as oncolytic viruses or other infectious or cytotoxic agents.

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Virus movements on the plasma membrane support infection and transmission between cells.

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