Author Description

This dissertation, "Study on Function of NS1 Protein in Influenza A Virus Replication and Vaccine Application of DelNS1 Viruses" by Min, Zheng,, was obtained from The University of Hong Kong (Pokfulam, Hong Kong) and is being sold pursuant to Creative Commons: Attribution 3.0 Hong Kong License. The content of this dissertation has not been altered in any way. We have altered the formatting in order to facilitate the ease of printing and reading of the dissertation. All rights not granted by the above license are retained by the author. Abstract: Influenza A virus causes significant morbidity and excessive mortality around the world every year and has precipitated four human pandemics during the past 100 years. While significant progress has been made in influenza research since the H5N1 outbreak in Hong Kong in 1997, many questions regarding how influenza virus replication is regulated remain to be answered. It is still not clear if a universal influenza vaccine may be a realistic option for preparedness of future emerging influenza viruses which pose a pandemic threat. Influenza virus non-structural protein 1 (NS1) is a virulence determinant with multiple functions; it is the major antagonist of innate immunity against influenza A virus and also plays an important role in regulating virus replication. More significantly, influenza A virus with NS1 gene deleted is highly attenuated and DelNS1 virus is being actively explored as a new live attenuated vaccine for both seasonal and pandemic influenza. To better understand the role of NS1 in the influenza A virus life cycle, I established three DelNS1 viruses from different strains to study the regulation of influenza virus replication and assess their potential for vaccine development. I found that the WSN-DelNS1, H7N9-DelNS1 and CA04-DelNS1 virus each acquired an M-A14U, M-G917A and NP-G346A mutation through passages either in MDCK, Vero or 10-day-old chicken embryonated eggs. Characterization of growth pr