This proposal requests support for a Keystone Symposia meeting entitled Pathogenesis of Influenza: Virus- Host Interactions, organized by Siamon Gordon, Malik Peiris and Kanta Subbarao, which will be held in Hong Kong, China from May 23 - 28, 2011. The mechanisms underlying the pathogenesis of influenza remain controversial. The direct cytopathic effects of viral replication, tissue tropism of the virus, viral-bacterial synergy, as well as innate host responses are inextricably linked and play roles to varying degrees in "seasonal," zoonotic and pandemic influenza, examples being the pandemics of 1918 and 2009 and H5N1 avian influenza. Animal models, though indispensible, have significant limitations with regard to physiological relevance to human disease. This meeting brings together researchers working on the virus, viral receptors and tissue tropism, innate and adaptive immunity, systems biology and clinical aspects of lung injury and host defense to address questions on the pathogenesis of influenza. The aim will be to integrate data from animal and human experimental models - both ex vivo and in vitro - as well as human disease to understand pathogenesis of influenza and how this may lead to effective interventions. As this symposium will take place in the aftermath of the first pandemic in 40 years, there will be a wealth of new knowledge as well as intense scientific interest in the subject. In view of the particular interest in influenza and other viral respiratory diseases generated in the Asia-Pacific region arising from the avian flu H5N1 and SARS experience, situating the meeting in Hong Kong will be particularly appropriate. PUBLIC HEALTH RELEVANCE: Pandemic influenza remains a major public health issue. There is an urgent need to better understand the origination and development - or pathogenesis - of severe viral infections that cause lung injury, and to explore novel therapeutic options targeting the host. The Keystone Symposia meeting on Pathogenesis of Influenza: Virus-Host Interactions aims to improve our understanding of determinants that facilitate inter- species transmission of influenza viruses.