Since 2005 Chikungunya fever has affected millions of people producing a high fever and a debilitating arthralgia which can persist for months and progress to chronic arthritis. Chikungunya virus has been associated with periodic outbreaks of human disease and is spread by mosquitoes. The current epidemic rose to prominence in 2005/6 following infection of >250,000 people on La Réunion. The virus rapidly spread to other islands in the Indian Ocean, India and SE Asia. Chikungunya cases in returning travellers have been reported. In summer 2007 a traveller from India to Italy initiated a locally transmitted outbreak which included one death from encephalitis. The mosquitoes transmitting this infection are spreading and increasing in Europe and could spread as far north as the British Isles. There are diagnostics tests, these require standardisation. The pathogenic mechanisms leading to myalgia, arthralgia, rare encephalitis and chronic arthritis are unknown precluding rational therapeutic intervention. There are no antivirals. There is no licensed vaccine. This project will integrate the expertise of EU laboratories with a long and strong track record of research on alphaviruses with EU laboratories that started work on CHIKV following the outbreak in La Réunion and laboratories from SE Asia working on this virus. The project will generate new molecular and cellular tools for research and applied studies, including high-throughput screening and vaccines; standardise, quality assure and distribute key diagnostic tests and develop new ones; determine virus genetic changes across time, geographical regions and species; discover interactions between virus and human cells to inform rational design of therapeutics; study immune responses in the chronic disease in humans, including whether virus persists in joints, the cell types involved and the relationship to immune responses; characterise rodent and non-human primate models of acute and chronic infection to further study the pathogenesis and provide models for antiviral and vaccine screens; screen libraries of characterized pharmaceutical and bioactive compounds for antiviral activity and develop a vaccine which at the end of this project is ready to enter clinical trials.