[YY-EEID US-UK XXXX] Evaluating how immunosuppression influences influenza A virus transmission and evolution in wild and domestic birds

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'Bird flu', caused by influenza A viruses (IAV), is a threat to the productivity of the poultry industry and to Public Health. Some waterbirds are naturally infected with IAVs, for example ducks, geese and swans, but the viruses can jump into poultry populations, with economically devastating consequences. Infectious bursal disease virus (IBDV) is an infection that can destroy the immune system of birds, causing what is known as immunosuppression. IBDV can worsen IAV infection in chickens: IBDV was found to increase the risk of IAV in chicken flocks, causing birds to shed IAV for longer, and reducing how effective IAV vaccines were. Taken together, these studies suggest that IAV from waterbirds will be able to transmit more easily in a chicken flock that has previously been exposed to IBDV. However, there has been no study of how IBDV affects IAV transmission and evolution in a poultry population, or on the contribution IBDV makes to the spread of other viral infections in waterbird populations. We plan to define how IBDV affects the IAV incubation period, the length of time birds shed IAV, the amount of IAV they shed, how much IAV it takes before they become infected, and the probablility of uninfected birds from becoming infected when placed in an infected group. This information will then be put into mathematical models that we have developed to define the effect of IBDV exposure on an IAV outbreak in chicken flocks. IBDV exposure may also change how the IAV evolves in the chicken, so we will determine the sequence of the IAV shed from the birds at different times after infection to see how the virus is changing over time. We also have access to a waterbird population that is subject to intense study and we have already identified IBDV in this population. We have over 2,000 samples from these birds stored that we plan to use to determine how many birds have been exposed to IBDV (the prevalence). We also plan to take more samples from a wider variety of waterbirds and from younger birds (that are more susceptible to IBDV) to investigate this further. We also plan to determine the extent to which the IBDV identified in this population causes disease and how destructive it is to the birds' immune systems. We will also determine the contribution IBDV makes to the spread of avian viruses in waterbirds by determining if there is a correlation with the number and amount of viruses shed and the presence of IBDV. The new information this project will generate will be used to define how much IBDV-induced immunosuppression contributes to the spread of IAVs in chickens and if it contributes to the spread of viruses in waterbirds. This can be used to influence policy- based decisions in the event of another IAV outbreak to improve control of the disease, for example by improving surveillance of IBDV and improving IBDV vaccination processes. In addition, we think this could be applied to other infections, and that diseases of the immune system could influence the spread and evolution of many viruses in wildlife and domestic animals.