| Abstract |
Influenza virus is a pathogen of great medical importance that has dominated the headlines many times in recent years. While seasonal epidemics of influenza exact significant socio-economic costs it is the emergence of new and novel strains of influenza virus that provide the most cause for concern. In 2009 the newly-emerged 'swine flu' strain of influenza virus quickly spread around the world causing a pandemic that taxed heath care systems throughout the world. Since 2003, fears over 'avian influenza' have lead to the culling of livestock and have significantly impacted the tourism industry in Asia. While avian influenza viruses are not as contagious for humans as swine-origin influenza viruses they are much more pathogenic, causing fatalities in 60 % of the cases. There is a significant fear that mutation of avian influenza viruses will occur, allowing them to spread from human-to-human with the efficiency of swine strains while retaining their high rates of mortality. This is highlighted by the recent emergence of H7N9 avian influenza viruses in China that have caused 130 cases of human infection in April 2013. The result of an emergent transmissible strain could be similar to that which occurred in 1918 when an influenza virus pandemic caused the death of 1 % of the world's population from 1918-1918. Thus, there is a continued need for the greater understanding of this deadly virus in the hopes of generating new methods to control and treat influenza virus infections. Influenza virus is an enveloped virus that obtains its lipid shell from the host cell's plasma membrane through a budding process. Inserted in the virus envelope are three proteins: hemagglutinin (which mediated viral entry into the host cell), neuraminidase (which is essential for the release of budded viruses) and the M2 protein (which is an ion channel protein that plays an important role during virus entry). Among the least understood events of the influenza virus lifecycle are the processes that mediate the formation of new viruses and their release from the host cell by membrane fission. Recently we have found a novel role for the influenza virus M2 protein in virus budding, the mediation of membrane fission. The aim of this research is to investigate the function of the influenza virus M2 protein to better understand its involvement in virus budding, allowing for a greater understanding of the complex process of influenza virus assembly and budding. The completion of this research project will show how the M2 protein is able to facilitate the budding of influenza viruses. However, this research has greater implications beyond the understanding of M2 protein functions. First, the creation of in vitro systems for investigating virus budding will be a valuable research tool allowing for other scientists to investigate the assembly and budding of multiple different viruses and protein complexes. Secondly, detailed understanding of the mechanism by which the M2 protein accomplishes its essential task of membrane fission will allow for the development of anti-influenza drugs targeting this function. Finally, better understanding of how the complex processes of virus assembly and budding are accomplished will advance the influenza virus field, generating essential knowledge about this medically important pathogen and providing many other new targets for anti-viral drug development. |