Research On Multi-scale HCV Models With Two Infection Modes And Immune Responses

Chronic hepatitis C is a significant threat to human health caused by hepatitis C virus(HCV)infection.HCV can infect liver cells through two modes,namely,cell-free and cell-to-cell.Immune responses are crucial in controlling or eliminating the disease by combating viral particles.Direct-acting antiviral agents(DAAs)are effective in treating HCV by directly interfering with different stages of the viral life cycle and reducing viral particle production.To gain a precise understanding of the intracellular viral RNA replication process,quantify antiviral effects,and optimize multi-drug combinations,we propose a multi-scale HCV model with two infection modes and immune responses.We also investigate the effects of cell-to-cell infection,immune responses,and drug treatment on HCV infection dynamics.In Chapter 2,we develop a multi-scale HCV model that considers two infection modes and antibody immune responses.We investigate the interaction between intracellular viral RNA replication and extracellular viral infection and derive expressions for the basic reproduction number and antibody immune response reproduction number.We demonstrate that the existence and global stability of the equilibria are completely determined by these numbers.We then consider the approximate solutions of the model during DAAs treatment and find that cell-to-cell infection brings the short-term approximate solution closer to the solution of the model,with the number of virus particles eventually remaining stable.Finally,through numerical simulation,we identify three stages in the decrease of viral load during therapy,with cell-to-cell infection mainly affecting the third stage and antibody immunity mainly affecting the first stage.In Chapter 3,we develop a multi-scale HCV model that considers two infection modes and two immune responses.We prove the well-posedness of the model and derive expressions for the basic reproduction number and four immune response reproduction numbers.We identify five equilibria,all of which are locally asymptotically stable.We then investigate the effects of cell-to-cell infection mode and immune responses on HCV infection dynamics through numerical simulation.Finally,we analyze the model during DAAs treatment and find that combined drug therapy has a stronger antiviral effect,and enhancing CTL immune response appropriately can effectively reduce viral load and prevent infection rebound.