Quantifying relative virulence: When μ max fails and AUC alone just isn’t enough

Abstract 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 (μmax) 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 (PIAUC), 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 (ISC) 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 ISC 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.