A Structural Atlas of TAP Inhibition by Herpesviruses and Poxviruses.
| Publication Type | Preprint |
| Authors | Lee J, Manon V, Chen J |
| Journal | bioRxiv |
| Date Published | 06/20/2025 |
| ISSN | 2692-8205 |
| Abstract | In the host-pathogen arms race, herpesviruses and poxviruses encode proteins that sabotage the transporter associated with antigen processing (TAP), thereby suppressing MHC-I antigen presentation and enabling lifelong infection. Of the five known viral TAP inhibitors, only the herpes simplex virus protein ICP47 has been structurally resolved. We now report cryo-electron microscopy structures of TAP in complex with the remaining four: BNLF2a (Epstein-Barr virus), hUS6 (human cytomegalovirus), bUL49.5 (bovine herpesvirus 1), and CPXV012 (cowpox virus), assembling a structural atlas of viral TAP evasion. Employing divergent sequences, folds and conformational targets, these viral inhibitors converge on a common strategy: they stall TAP from the alternating access cycle, precluding peptide entry into the ER and shielding infected cells from cytotoxic T-cell surveillance. These findings reveal striking functional convergence and provide a structural framework for rational antiviral design. |
| DOI | 10.1101/2025.06.19.660632 |
| PubMed ID | 40611894 |
| PubMed Central ID | PMC12224542 |