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

禽流感是由甲型流感病毒(IAV)引起的，对家禽业的生产力和公共卫生构成威胁。一些水鸟自然感染了IAV，例如鸭子、鹅和天鹅，但病毒可能会进入家禽种群，造成灾难性的经济后果。传染性法氏囊病病毒(IBDV)是一种可以破坏鸟类免疫系统的感染，导致所谓的免疫抑制。IBDV可以加重鸡的IAV感染：IBDV被发现增加了鸡群中IAV的风险，导致禽类排出IAV的时间更长，并降低了IAV疫苗的有效性。综上所述，这些研究表明，来自水鸟的IAV将能够更容易地在以前接触IBDV的鸡群中传播。然而，还没有关于IBDV如何影响家禽种群中IAV传播和进化的研究，也没有关于IBDV在水鸟种群中对其他病毒感染传播的贡献的研究。我们计划确定IBDV如何影响IAV潜伏期，鸟类排出IAV的时间长度，它们排出的IAV量，在它们被感染之前需要多少IAV，以及未感染的禽类在被置于感染组时被感染的可能性。然后，这些信息将被输入到我们开发的数学模型中，以确定IBDV暴露对鸡群中IAV暴发的影响。IBDV暴露也可能改变IAV在鸡体内的进化方式，因此我们将确定感染后不同时间从禽类身上流出的IAV的序列，看看病毒如何随着时间的推移而变化。我们还可以接触到正在进行密集研究的水鸟种群，我们已经在这个种群中发现了IBDV。我们有超过2000份这些禽类的样本，我们计划用这些样本来确定有多少禽类接触了IBDV(流行率)。我们还计划从更多种类的水鸟和更年轻的鸟类(更容易感染IBDV)中提取更多样本，以进一步调查这一问题。我们还计划确定在这个种群中发现的IBDV导致疾病的程度，以及它对鸟类免疫系统的破坏性。我们还将通过确定IBDV在水禽中传播的病毒数量和数量与IBDV的存在是否相关，来确定IBDV对禽类病毒在水禽中传播的贡献。该项目将产生的新信息将用于确定IBDV诱导的免疫抑制在多大程度上有助于IAV在鸡中的传播，以及它是否有助于病毒在水鸟中的传播。这可用于在再次爆发IAV时影响基于政策的决定，以改善对疾病的控制，例如通过改进对IBDV的监测和改进IBDV疫苗接种程序。此外，我们认为这可能适用于其他感染，免疫系统疾病可能会影响许多病毒在野生动物和家养动物中的传播和进化。

'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.