Quantifying the dynamics of viruses and the cellular immune response of the host

Abstract

Infections can be caused by viruses, which attack certain cells within an infected host. However, the immune system of the host has evolved remarkable defense mechanisms that counter against an infection. In particular, so-called cytotoxic T lymphocytes can recognize and eliminate infected cells. This thesis makes use of mathematical models and computer simulations to describe the dynamics of a virus population and the cellular immune response within an infected host. Such research is of critical importance to better understand the nature of viral infections. In the beginning, questions on the HIV replication rate are addressed. It is investigated how rapid infected cells produce new virus particles and how rapid they die. It has been known that after HIV-infected patients start with antiretroviral drug treatment, the concentration of virus in the blood decreases rapidly. This observation has led to the conclusion that HIV-infected cells are short lived and that they die one to two days after they have been infected. Based on a new analysis, the thesis shows that HIV-infected cells might even live shorter than previously anticipated. Further, several models that describe the dynamics of viruses in presence of a cellular immune response are presented. They are used to investigate the ability of the immune response to suppress the replication of the virus. In the case of the chronic infection with HIV, it is shown how the virus can mutate and avoid recognition and elimination by the immune response. This process is attributed to the failing of HIV-infected patients to control the infection and it is shown how rapid the virus can escape the immune response. Finally, the thesis deals with viral infections in different host species, such as mice, macaques and humans. Therefore, it is discussed as to whether the findings on the influence of the immune response on the viral replication can be generalized. Although some differences in the results can be attributed to the body weight of the host species, additional research is needed to shed more light on the question whether the nature of viral infections is affected by the size of their host