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.