Characterisation of host virus interactions.

HIV-1, the virus that causes most AIDS cases, has evolved to slip past a human protein called tetherin that would otherwise trap and disable it. This project will map exactly how HIV-1 and related viruses evade this and other innate immune defences. The problem is that while some lentiviruses—a family that includes HIV—only infect certain primates without causing widespread disease, HIV-1 M has become a global pandemic. Researchers suspect that differences in how these viruses interact with human restriction factors determine which ones can spread. But the molecular details remain poorly understood, especially for tetherin, the most recently discovered restriction factor. This is fundamental science. The team will combine molecular biology, structural studies, and evolutionary analysis to reveal how host proteins dictate which viruses can infect humans. They will also search for entirely new restriction factors in human macrophages, the immune cells that HIV targets. Understanding these molecular handshakes could eventually inform strategies to block viral entry or boost natural defences. Past discoveries of restriction factors have already led to insights for antiviral drug design, though any practical applications from this work remain years away.