Nucleic Acid Sensing by Innate Immune Receptors

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We are trying to work out how the immune system is activated in virus infection and inflammatory disease. Cells infected by virus respond by producing anti-viral factors, which block viral replication and help to control infection. We are interested in a cell molecule called RIG-I, which detects infection with viruses such as influenza A virus. RIG-I recognizes the presence of viral genomes made of RNA. However, normal cells also contain RNA as this is the ‘messenger’ molecule that allows the DNA genes of cells to be copied and translated into protein. How, then, can RIG-I distinguish between the RNA of the cell and the RNA of the virus? The answer lies in a structure called a ‘cap’ found at the starting point of cellular RNAs. Viral RNA genomes do not have this ‘cap’ and RIG-I specifically responds only to RNAs lacking this structure. This is why only cells infected by viruses produce anti-viral factors. By working out how RIG-I and other receptors detect infection with a variety of viruses we aim to understand how this type of immune response is controlled. In a second line of research, we are interested in inflammatory diseases such as Aicardi-Goutieres syndrome that result of the anti-viral pathways being triggered aberrantly in the absence of infection. We hope to determine how deregulation of these pathways can result in disease and find ways of controlling inappropriate inflammatory responses.