BPIFA1: from anti-viral peptide to immunomodulator

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The respiratory tract is under constant attack from microbial invasion. The cells lining the respiratory tract have therefore evolved to secrete molecules that defend against infection. The BPIFA1 molecule is produced continuously in the respiratory tract of mammals. Using genetically modified mice that are unable to produce BPIAF1, we have shown that it helps defend against influenza A virus by inhibiting infection of cells lining the respiratory tract and also by helping the generation of immunity against influenza. BPIAF1 is therefore a critical factor in the response to influenza. The aims of this project are to:1. Discover the precise way that BPIFA1 interacts with virus and inhibits infection of cells. This will involve making recombinant forms of BPIFA1 and measuring their effectiveness at blocking virus infection.2. Discover exactly how BPIFA1 affects the immune response to influenza. This will involve comparing the progress of viral infection in genetically modified mice deficient in BPIFA1 with normal mice. The response of individual cells and components of the immune response will then be measured to determine the mechanism of action3. Determine if BPIFA1 can improve influenza vaccination. The results will significantly enhance our understanding of fundamental aspects of defence to virus infection as well as aspects of respiratory biology. The research will be carried out at the Universities of Liverpool and Sheffield by a multi-disciplinary team comprising members of the Medical and Veterinary Faculties using well-equipped facilities currently situated at these sites. In view of the recognised limitations of influenza virus vaccines understanding detailed mechanisms of action offers a very real alternative to address the need for "universal" influenza virus therapeutics, Importantly, understanding how BPIFA1 modulates the immune response to IAV may lead to the production of improved vaccination strategies