Quantifying relative virulence: when μ_max fails and AUC alone just is not enough

A challenge in virology is quantifying relative virulence (V_R) between two (or more) viruses that exhibit different replication dynamics in a given susceptible host. Host growth curve analysis is often used to mathematically characterize virus-host interactions and to quantify the magnitude of detriment to host due to viral infection. Quantifying V_R using canonical parameters, like maximum specific growth rate (μ_max), can fail to provide reliable information regarding virulence. Although area-under-the-curve (AUC) calculations are more robust, they are sensitive to limit selection. Using empirical data from Sulfolobus Spindle-shaped Virus (SSV) infections, we introduce a novel, simple metric that has proven to be more robust than existing methods for assessing V_R. This metric (I_SC) accurately aligns biological phenomena with quantified metrics to determine V_R. It also addresses a gap in virology by permitting comparisons between different non-lytic virus infections or non-lytic versus lytic virus infections on a given host in single-virus/single-host infections.