Background:Influenza and coronavirus have been repeatedly causing pandemic recently. Like theInfluenza A/H7N9 virus has caused five epidemics in China since its first detection inEast China in 2013. In 2017, the previously low pathogenic avian influenza (LPAI) H7N9virus underwent mutation in its haemagglutinin to give to a highly pathogenic avianinfluenza (HPAI) virus causing 32 human cases and potentially poses a threat to animaland human health. More recently, the SARS-CoV-2 pandemic has been heavily affecting theworld. Therefore an effective risk assessment platform is urgently required for betterpandemic preparation.Hypothesis:The tissue tropism and pathogenesis of a newly emerged infectious viruses, like thehighlypathogenic influenza, like H7N9 and coronavirus, like SARS-CoV-2 would be differentfrom that of their low pathogenic subtype and it would infect and replicate the humanrespiratory system more efficiently.Because of its resistance to oseltamivir for influenza and no effective antiviral forcoronavirus, investigators therefore propose to set up an novel and effective riskassessment platform for emerging infectious viruses.Experimental Design:The tissue tropism and viral replication kinetics of a HPAI and LP influenza andcoronavirus will be determined in ex vivo cultures of human brain and compared with theirLP subtype. The replication competence and innate immune responses of influenza andcoronavirus will be studied and compared with other LP virus in in vitro cultures ofhuman brain cells and human microvascular endothelial cells (HMVEC) both isolated fromhuman brain tissues.Expected outcomes:HPAI influenza and coronavirus particularly SARS-CoV-2 will infect and replicate thehuman brain tissues and cells more efficiently than their LP subtype. Besides, HPAIinfluenza and SARS-CoV-2 will induce dysregulated host innate immune response than the LPsubtype.