The early inflammatory response to virulent and avirulent influenza viruses

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Innate immune mechanisms are vital components of host defences against pathogens. In this proposal I aim to investigate the particular mechanisms that operate in early defence against influenza virus infection and compare the ability of virulent and avirulent virus strains to (i) be recognized by components of the innate immune system, and (ii) to trigger an early inflammatory response to infection. It is anticipated that virulent virus strains have adapted to avoid recognition by innate cells such as macrophages. By avoiding this route of uptake and destruction, the virus is free to infect and replicate in other cells of the respiratory tract. Furthermore, by evading macrophage entry, the virus avoids triggering the release of early inflammatory mediators from these cells and this may affect both the speed and the magnitude of the subsequent inflammatory response. This study will contribute to a greater understanding of factors involved in initiating and regulating inflammation in the respiratory tract following viral infection. Furthermore, the findings may provide new insights into mechanisms of virulence of influenza and other enveloped viruses.