Hepatitis C virus (HCV) infection is one of the most significant health problems affecting humans. In addition, HCV infection is the most common cause of liver fibrosis and cirrhosis. The infected cells activate the immune response, and interferon is released by the infected cells and activates the JAK-STAT signaling pathway, a chain of biochemical reactions involved in the immune response, leading to the transcription of hundreds of interferon-stimulated genes (ISGs). The ISG products exert numerous antiviral functions. Recently, it has been reported that seven ISGs show a significant anti-HCV response. From a mathematical modeling point of view, this study aimed to investigate whether ISG overexpression leads the system to an irreversible clearance state. A stochastic model for the molecular machinery involved in cells infected with HCV and the immune response was used to reproduce viral dynamics. The model considers seven ISG-encoded proteins. Our results suggest that the IFITM1 protein plays an essential role in the hepatitis dynamics obtaining the clearance state when overexpressed.
Elsevier, Feedback Control for Personalized Medicine, 2022, Pages 173-188