Quantifying relative virulence: When μmaxfails and AUC alone just isn’t enough

A bstract One of the more challenging aspects in quantitative virology is quantifying relative virulence between two (or more) viruses that have different replication dynamics in a given susceptible host. Host growth curve analysis is often used to detail virus-host interactions and to determine the impact of viral infection on a host. Quantifying relative virulence using canonical parameters such as maximum specific growth rate (μ max ) can fail to provide accurate information regarding experimental infection, especially for non-lytic viruses. Although area-under-the-curve (AUC) can be more robust by through calculation of a percent inhibition (PI AUC ), this metric can be sensitive to limit selection. In this study, using empirical and extrapolated data from Sulfolobus Spindle-shaped Virus (SSV) infections, we introduce a novel, simple metric that is proven to be more robust and less sensitive than traditional measures for determining relative virulence. This metric ( I SC ) more accurately aligns biological phenomena with quantified metrics from growth curve analysis to determine trends in relative virulence. It also addresses a major gap in virology by allowing comparisons between non-lytic single-virus/single-host (SVSH) infections and between non-lytic versus lytic virus infection on a given host. How I SC may be applied to polymicrobial infection – both coinfection of a host culture and superinfection of a single cell with more than one virus (or other pathogen type) is a topic of ongoing investigation.