Structural basis for innate immune suppression by Rift Valley fever phlebovirus

Rift Valley fever (RVF) is a mosquito-borne disease that is endemic to the Rift Valley in Africa. It affects mammals such as cattle and goats, causing abortion storms and neonatal death, but it can also affect humans, and in some cases, cause haemorrhagic fever, leading to death. Additionally, due to climate change, the mosquitoes that carry this virus are spreading to the Middle East and Europe. There is currently no vaccine for human RVF. The main virulence factor of Rift Valley fever virus (RVFV) is thought to be its NSs protein, which forms filaments in the host cells' nuclei in vivo, which bind to TFIIH and supress the interferon (IFN) pathway. My project will use cryo-ET, a structural technique, to view the mechanism of how these filaments form and how the IFN pathway is suppressed in situ, with the hopes of this information making it possible to design a drug or vaccine that targets RVFV NSs.