Impacts of genetics, environment and noise on virus growth

John Yin (October 26, 2011)

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The dynamics of a virus infection within its host is governed at its earliest stages by processes at the molecular and cellular scale. We are developing cell-culture measurements and computational models to better understand how these and other processes contribute to the early dynamics of virus growth and infection spread. As a model system we study vesicular stomatitis virus (VSV), a rabies-like RNA virus, growing on BHK cells. Established single-cycle measures of virus growth within infected cells provide population averages, which mask potential cell-to-cell variation. We used fluorescence-activated cell sorting to isolate single cells infected by single particles of a recombinant VSV expressing green fluorescent protein. Measured virus yields spanned a broad range from 8000 to below the detection limit of 10 infectious virus particles per cell. Viral genetic variation and host-cell cycle differences were unable to fully account for the observed yield differences. Computer simulations of the VSV dynamics within an infected cell suggest a potential role for stochastic gene expression to the observed yield variation. These studies are currently being extended to study the kinetics of virus production from individual infected cells.