Fig. 5

ICP47 function during HSV infection. a Intracellular antigenic peptides, mainly generated by the proteasome, are transported into the endoplasmic reticulum by the TAP and then loaded onto the nascent MHC I molecules, which are exported to the cell surface and present peptides to the immune cells. Cytotoxic T lymphocytes recognize and kill the infected cells by granzyme and perforin. b ICP47 can preclude peptide binding and traps TAP in an inward-facing conformation. Binding of ICP47 stabilizes the inward-facing conformation, and thus prevents TAP from transitioning to an outward-facing state, resulting in the emergence of empty carrier MHC I molecules. Therefore, CD8⁺ T cells could not recognize them, and HSVs could avoid the immune responses. We hypothesize that c-Rel bind to its US12 TRS, and enhance US12 (ICP47) expression, leading to HSV-1 immune evasion and HSV-1 encephalitis