Modelling the dynamics of LCMV infection in mice: II. Compartmental structure and immunopathology

In this study, we develop a mathematical model for analysis of the compartmental aspects and immunopathology of lymphocytic choriomeningitis virus (LCMV) infection in mice. We used sets of original and published data on systemic (extrasplenic) virus distribution to estimate the parameters of virus growth and elimination for spleen and other anatomical compartments, such as the liver, kidney, thymus and lung as well as transfer rates between blood and the above organs. A mathematical model quantitatively integrating the virus distribution kinetics in the host, the specific cytotoxic T lymphocyte (CTL) response in spleen and the re-circulation of effector CTL between spleen, blood and liver is advanced to describe the CTL-mediated immunopathology (hepatitis) in mice infected with LCMV. For intravenous and "peripheral" routes of infection we examine the severity of the liver disease, as a function of the virus dose and the host's immune status characterized by the numbers of precursor and/or cytolytic effector CTL. The model is used to predict the efficacy of protection against virus persistence and disease in a localized viral infection as a function of the composition of CTL population. The modelling analysis suggests quantitative demands to CTL memory for maximal protection against a wide range of doses of infection with a primarily peripheral site of virus replication without the risk of favoring immunopathology. It specifies objectives for CTL vaccination to ensure virus elimination with minimal immunopathology vs. vaccination for disease.