Virulence of a virus: How it depends on growth rate, effectors, memory cells, and immune escape.

Abstract A viral strain may infect a host, proliferate rapidly, become controlled by immune reactions, and eventually be eliminated from the body. The virulence, or the magnitude of harm to the host due to infection, depends on the abundance and duration of the viral strain in the body, and the importance of the damaged tissue of the host. In this study, we investigated how the cumulative viral load (time-integral of the number of infected cells) depends on various factors, such as the viral growth rate, the effectiveness of immune cells to kill infected cells, speed of immune activation, formation of memory cells, and longevity of immune cells. In addition, viruses may produce a mutant with different antigen types, escape the immune reaction targeting the original type, and inflate virulence. We succeeded in deriving simple and explicit formulas of the virulence in four different parameter regions. We found that, in some parameter region, enhancing memory cells is very effective in suppressing virulence, but direct activation of immune effector cells is not effective; while the opposite is the case in other regions. The result could be important in designing drug suppressing virus effectively. Additionally, we discussed the reported correlation between virulence and molecular evolution rate.