MODELING OF IMMUNE RESPONSES IN INFECTIOUS DISEASES

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. There have been many recent developments of laboratory techniques that allow the quantification of immune responses against infections. In turn, the availability of these new quantitative data makes possible, and indeed necessitates, the development of new theoretical quantitative models to help interpret them. In this proposal, we are developing models of immune responses against viral infections. We specifically address two important infections, hepatitis B virus (HBV) and hepatitis C virus (HCV) infection. Both these viruses infect liver cells, and may lead to chronic infection and serious liver disease, which is thought to be mostly due to the immune response. Conversely, the initial immune response is crucial in determining the outcome of infection - whether an individual eradicates infection or becomes chronically infected. However, the dynamics and quality of the early immune response are different in these viruses. We are developing mathematical models informed by the new data available, which will be used to help interpret the data and, potentially, to plan new experiments. Our models include the dynamics of the virus and immune cell populations, and initially are based on very successful approach used to study human immunodeficiency virus (HIV). Comparative modeling of the immune responses against viruses with similar, but not identical, pathologies, for which there is a growing amount of experimental data, will help us understand not only these diseases better, but also immunity against viruses in general.