Effects of HIV-1 Proteins on the Fas-Mediated Apoptotic Signaling Cascade: A Computational Study of Latent CD4+ T Cell Activation

摘要

We present a new model for simulating Fas-induced apoptosis in HIV-1-infected CD4+ T cells. Moreover, the reactivation of latently infected cells is explored. The work, an extension of our previous modeling efforts, is the first attempt in systems biology for modeling the Fas pathway in the latently infected cells. These enigmatic cells are considered the last barrier in the elimination of HIV infection. In building the model, we gathered what reaction rates and initial conditions are available from the literature. For the unknown constants, we fit the model to the available information on the observed effects of HIV-1 proteins in activated CD4+ T cells. We provide results, using the Nondeterministic Waiting Time (NWT) algorithm, from the model, simulating the infection of activated CD4+ T cells as well as the reactivation of a latently infected cells. These two model versions are distinct with respect to the initial conditions - multiplicities and locations of proteins at the beginning of the simulation.