Mathematical Modeling and Quantification of Viral Entry Assays

University Of California-Los Angeles, Los Angeles CA

Investigators

Abstract

The ability to quantitatively define and measure how infective different strains of viruses are towards live cells is critical for the development of antivirals. Surprisingly, there exists no standardized way to measure and compare infectivities across viral strains and under different experimental conditions. This research will develop the quantitative framework needed and quantify existing experimental measurements of infectivity. Most importantly, the models and analysis tool will allow quantitative comparison of existing infectivity data. Such comparisons will facilitate the development of antivirals that block viral entry, or complex antibodies that neutralize virus particles. The research is independent of the particular virus under consideration and may be feasibly extended to bacterial pathogens. The first component of the research will be to model, under typical experimental conditions, the physical process of viral entry into cells. Specifically, the investigators aim to understand the effects of (i) protocols such as centrifugation that bring virus particles close to their target cells, (ii) the reporter system used to count the number of cells infected, and (iii) the different parameters, such as temperature, duration of exposure, and antiviral concentrations under which the assays were performed. A model for how these variables affect the measured infectivities will allow different experiments, performed in different laboratories under different conditions, to be compared with each other. The second component of the proposed research involves implementing the models for viral entry into a web-based data analysis tool that will be constructed. It is anticipated that this tool will aid virologists in their interpretation of large scale infectivity data in terms of biological and mechanistic attributes of the viruses.