BPIFA1: from anti-viral peptide to immunomodulator

呼吸道经常受到微生物的侵袭。因此，呼吸道的细胞已经进化成分泌抵抗感染的分子。BPIFA 1分子在哺乳动物的呼吸道中持续产生。使用不能产生BPIAF 1的转基因小鼠，我们已经证明它有助于通过抑制呼吸道细胞的感染来防御甲型流感病毒，并有助于产生针对流感的免疫力。因此，BPIAF 1是流感应答的关键因素。该项目的目标是：1。发现BPIFA1与病毒相互作用并抑制细胞感染的精确方式。这将涉及制造BPIFA1的重组形式并测量它们在阻断病毒感染方面的有效性。了解BPIFA 1如何影响对流感的免疫反应。这将涉及比较BPIFA 1缺陷的转基因小鼠与正常小鼠的病毒感染进展。然后将测量单个细胞的反应和免疫反应的组分，以确定作用机制3。确定BPIFA1是否可以改善流感疫苗接种。这些结果将大大提高我们对病毒感染防御的基本方面以及呼吸生物学方面的理解。该研究将在利物浦和谢菲尔德大学由一个多学科小组进行，该小组由医学和兽医学院的成员组成，使用目前位于这些地点的设备齐全的设施。鉴于流感病毒疫苗的公认局限性，了解详细的作用机制提供了一个非常真实的替代方案，以解决对"通用"流感病毒治疗剂的需求。重要的是，了解BPIFA 1如何调节对IAV的免疫应答可能导致产生改进的疫苗接种策略

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