Infected cell protein 47 (ICP47)

Infected cell protein 47 (ICP47) is an immediate-early protein produced by Herpes Simplex Virus (HSV-1 and HSV-2) that serves as a potent immunoevasin [1, 8]. Its primary biological function is to inhibit the host's adaptive immune response by binding with high affinity to the Transporter associated with Antigen Processing (TAP) complex [6, 13]. By occupying the peptide-binding site of the TAP1-TAP2 heterodimer, ICP47 blocks the translocation of viral antigenic peptides from the cytosol into the endoplasmic reticulum (ER) [14, 23]. This prevents the loading of these peptides onto MHC class I molecules, which are consequently retained in the ER and fail to reach the cell surface [1, 16]. As a result, HSV-infected cells are effectively masked from detection and destruction by cytotoxic CD8+ T lymphocytes, facilitating viral persistence and contributing to neurovirulence [9, 10]. In the field of oncology, ICP47 is a key target for genetic deletion in the development of oncolytic viruses, such as Talimogene laherparepvec (T-VEC) [17, 18]. The removal of the ICP47 gene from these therapeutic viruses restores MHC class I expression in infected tumor cells, thereby enhancing the induction of a systemic anti-tumor immune response [20, 26].

Other names

US12 proteinImmediate-early protein IE12Immediate-early-5Vmw12Infected cell protein 47 (ICP47)

Binds to the peptide-binding site of the TAP1-TAP2 heterodimer, preventing the translocation of antigenic peptides into the endoplasmic reticulum and subsequent MHC class I presentation.