383112 Quantification and Modeling of Infection Spread in the Presence of Virus-like Defective Interfering Particles

Monday, November 17, 2014: 4:27 PM
214 (Hilton Atlanta)
Fulya Akpinar, Bahar Inankur and John Yin, Chemical and Biological Engineering, University of Wisconsin-Madison, Madison, WI

Defective interfering particles (DIPs) are virus mutants lacking genes essential for the production of viral proteins, but able to divert the viral proteins produced by an infectious virus, and thus, interfere with infectious virus production. Their ability to interfere with normal viral infections makes DIPs a useful tool to probe virus-cell interactions. Moreover, the accumulating evidence about their presence in natural infections and the increasing interest in vaccine formulations using DIPs highlight the need for understanding of the effect of DIPs on infection kinetics and on spread behavior of infection. In view of this, in this study, we analyzed the infection propagation behavior of a recombinant vesicular stomatitis virus (VSV) expressing red fluorescent protein (RFP) on cell monolayers in the presence of DIPs associated with the same virus strain. Quantification of infection spread behavior using multichannel fluorescence microscopy imaging and custom developed image processing workflow revealed the emergence of spread phenotypes with varying concentrations of DIPs. To further analyze the contribution of intracellular and extracellular processes involved in emergence of these different phenotypes, we developed a data-driven multilevel cellular automata model. The model incorporates the experimentally determined correlations between DIP input and single-cell level infection kinetics as well as the extracellular processes such as diffusion and adsorption, and therefore captures the stochasticity of the infection spread at multiple levels. Overall, this study provides insights about the interactions between viruses and DIPs that can guide future studies of the virally infectious disease progression in the presence of naturally occurring DIPs or DIPs administered as a vaccine component.

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