File:Viruses-13-00861-g001-550 (1).webp

English: Figure 1. Proposed mechanisms of liver injury mediated by HAV. (A) During HAV infection, the virus activates CD8+ T cells, generating virus-specific CD8+ T cells. Activated virus-specific CD8+ T cells are differentiated into effector cytotoxic T lymphocytes that specifically kill virus-infected cells, thus contributing to liver injury. (B) In patients with hepatitis A, high levels of IL-15 in the serum activate non-virus-specific CD8+ T cells, which are capable of lysing both infected and uninfected hepatocytes. (C) High levels of IL-18 have been detected in both macrophages and hepatocytes in IL-18BP-deficient-patients with fulminant hepatitis A. Due to lack of neutralizing activity against IL-18, excessive and uncontrolled IL-18 activates NK cells, which subsequently mediate the lysis of both infected and uninfected hepatocytes. (D) In patients with severe hepatitis A, HAV seems to activate NKT cells in a TIM-1 dependent manner. HAV-infected cells had higher cytotoxic activity in NKT cells carrying the longer form of TIM-1 than in NKT cells harboring the wild type TIM-1, thereby contributing to liver injury. Apoptosis of HAV-infected hepatocytes mediated by MAVS-IRF3/IRF7-dependent signaling has also been implicated in liver injury in a murine model of HAV [10].