Modeling and Simulation of HIV-1 Intracellular Replication

Modeling HIV infection has a long history since 1980s when HIV was discovered and the AIDS symptomes were first observed. In recent decades, treating Human Immunodeficiency Virus infection and AIDS has been the main research topic of many experiments in laboratories around the world. In spite of the broad effort in designing antiretroviral drugs for treating HIV patients, there is still no specific vaccine or drug available to completely block the virus replication. Many mathematical and computational models have been developed to investigate the complexity of HIV dynamics, immune response and drug therapy. The objective of this thesis is to model the intracellular replication cycle of HIV-1. The model is basically designed to study HIV replication inside a single cell before initiation of drug therapy. Two modeling approaches have been used to implement the virus replication model:Rate-limited approach and diffusion-limited approach. Results of the model are discussed based on the number of cDNA created and integrated into the host cell DNA, the number of viral mRNA transcribed, and the amount of translated viral proteins after a single round of virus replication. Model validation is demonstrated graphically and quantitatively based on comparison between simulation results and available experimental data. A sensitivity analysis is also performed on some of the parameters used in the model. This analysis helps us to determine which steps, in the viral replication process, are more sensitive and uncertain. These results also indicate which parameters are critical in the replication process and which parameters are less sensitive. Results obtained from the simulation give insights about the detail of HIV replication dynamics inside the cell at protein level. Therefore the model can be used for future studies of HIV intracellular replication in vivo and drug treatment.