Poxvirus immune evasion strategies.

Vaccinia virus, the weapon that eradicated smallpox, is still hiding tricks from the immune system, and this research will hunt them down. The problem is that even a successful vaccine leaves gaps in our understanding. Vaccinia virus (VACV) carries dozens of proteins that actively sabotage the host’s immune response, but many of these molecular weapons remain unidentified, and the mechanisms of known ones are poorly understood. This programme will systematically identify new VACV immune-evasion proteins, work out how they block host defences, and determine their three-dimensional structures. It will also investigate how host cells detect double-stranded DNA in the cytoplasm—a key alarm system for viral infection—and how VACV disables that alarm. This is fundamental science, not applied vaccine development. The immediate payoff is a deeper understanding of virus-host conflict at the molecular level. If successful, it will reveal the precise biochemical moves viruses use to win early battles against our cells. That knowledge could eventually guide the design of more immunogenic poxvirus-based vaccines or therapies for other viruses that use similar evasion tactics—but those applications are years away. For now, the value lies in mapping the battlefield.