Mechanisms of helminth induced antiviral immunity to RSV infection

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In babies and toddlers worldwide, respiratory syncytial virus (RSV) is the most common cause of a type of chest infections called bronchiolitis and causes a severe lung inflammation. 2% of all babies in the UK have to be admitted to hospital with RSV bronchiolitis and some of them develop very severe and sometimes life threatening disease. This happens particularly when very high numbers of virus particles are present after infection. Death due to RSV is rare in the UK, but it is a significant problem in developing countries. Due to treatment costs and costs for the wider society (e.g. days lost at work for parents/ carers) RSV is responsible for a major financial burden. Despite all of this, no specific treatment or effective, widely available preventative interventions exist and novel approaches are urgently required. Palivizumab, a monoclonal antibody to RSV can prevent hospital admissions by about 50%, but due to high cost its use is limited to small groups of high risk infants in affluent countries. We have recently found that infection with a gut parasite worm can reduce the number of viral particles in the lungs in a mouse model of RSV infection and block the accumulation of the immune system cells that drive inflammation. In worm-infected mice, we also found an increased expression of antiviral genes that are involved in containing and eliminating the virus. These observations suggest that a worm infection of the gut can lead to an antiviral state in the lung which reduces numbers of viral particles, immune cell responses, inflammation, and disease severity in RSV infection. Here, we will initially use our mouse model to study which cells and/or substances of the mouse's immune system are responsible for the antiviral effects during parasite worm infection and whether these cells and/or substances can be used instead of worm infection to reduce the severity of RSV infection. We will also use this model to test whether worm-derived products alone, rather than the full process of worm infection, are sufficient for the desired antiviral effects. To find out if gut parasite worm infections also lead to antiviral effects against RSV in humans we will study children in Uganda where these worm infections are still common. We will take small samples from the inner lining of the nose, where RSV initially grows, and blood samples to compare the levels of antiviral genes (with and without RSV exposure in the laboratory) between children with and without gut worm infection. These studies will let us find out which immune cells or substances that arise during worm infection, lead to an antiviral state in the lung and whether these substances or cells will be promising new targets to develop preventive treatment for severe RSV bronchiolitis.