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

[YY-EEID US-UK XXXX] 评估免疫抑制如何影响野生和家禽中甲型流感病毒的传播和进化

• 批准号: BB/T008806/1
• 负责人: Holly Shelton
• 金额: $ 77.26万
• 依托单位: The Pirbright Institute
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2019
• 资助国家: 英国
• 起止时间: 2019 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FT008806%2F1
• 关键词: YY; EEID; US; UK; XXXX

'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.

由甲型流感病毒（IAV）引起的“禽流感”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，鹅和天鹅，但病毒可以跳跃到家禽种群中，造成经济上的破坏性后果。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可使鸡的IAV感染恶化：发现IBDV增加鸡群中IAV的风险，导致鸟类更长时间地脱落IAV，并降低IAV疫苗的有效性。总之，这些研究表明，来自水鸟的IAV将能够更容易地在先前暴露于IBDV的鸡群中传播。然而，还没有研究IBDV如何影响IAV在家禽种群中的传播和进化，或者IBDV对其他病毒感染在水鸟种群中传播的贡献。我们计划确定IBDV如何影响IAV的潜伏期，鸟类脱落IAV的时间长度，它们脱落的IAV数量，在它们被感染之前需要多少IAV，以及未感染的鸟类在被置于感染组时被感染的概率。然后将这些信息输入我们开发的数学模型，以确定IBDV暴露对鸡群中IAV爆发的影响。暴露于IBDV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鸟类中脱落的IAV序列，以了解病毒如何随时间变化。我们也有机会接触到一个正在进行深入研究的水鸟种群，我们已经在这个种群中鉴定出了IBDV。我们储存了2,000多份来自这些禽类的样本，我们计划用这些样本来确定有多少禽类暴露于IBDV（患病率）。我们还计划从更广泛的水鸟和更年轻的鸟类（更容易感染IBDV）中采集更多样本，以进一步研究这一点。我们还计划确定在该种群中鉴定的IBDV引起疾病的程度以及它对鸟类免疫系统的破坏程度。我们还将通过确定是否存在与病毒脱落的数量和量以及IBDV的存在相关性来确定IBDV对水鸟中禽类病毒传播的贡献。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。这可用于在另一次IAV爆发的情况下影响基于政策的决定，以改善疾病的控制，例如通过改善对IBDV的监测和改善IBDV疫苗接种过程。此外，我们认为这可以应用于其他感染，免疫系统疾病可以影响野生动物和家畜中许多病毒的传播和进化。

项目成果

Birnaviridae virus factories show features of liquid-liquid phase separation, and are distinct from paracrystalline arrays of virions observed by electron microscopy

双RNA病毒科病毒工厂表现出液-液相分离的特征，与电子显微镜观察到的病毒颗粒的旁晶阵列不同

• DOI: 10.1101/2021.11.16.468875
• 发表时间: 2021
• 作者: Reddy V

Birnaviridae Virus Factories Show Features of Liquid-Liquid Phase Separation and Are Distinct from Paracrystalline Arrays of Virions Observed by Electron Microscopy.

• DOI: 10.1128/jvi.02024-21
• 发表时间: 2022-03-23
• 期刊: Journal of virology
• 影响因子: 5.4
• 作者: Reddy VRAP;Campbell EA;Wells J;Simpson J;Nazki S;Hawes PC;Broadbent AJ
• 通讯作者: Broadbent AJ

Antigenic Characterization of Human Monoclonal Antibodies for Therapeutic Use against H7N9 Avian Influenza Virus.

• DOI: 10.1128/jvi.01431-22
• 发表时间: 2023-01-31
• 期刊: Journal of virology
• 影响因子: 5.4

Impact of host age on viral and bacterial communities in a waterbird population.

• DOI: 10.1038/s41396-022-01334-4
• 发表时间: 2023-03
• 期刊: ISME JOURNAL
• 影响因子: 11
• 作者: Hill, Sarah C.;Francois, Sarah;Theze, Julien;Smith, Adrian L.;Simmonds, Peter;Perrins, Christopher M.;van der Hoek, Lia;Pybus, Oliver G.
• 通讯作者: Pybus, Oliver G.

Seasonal dynamics of the wild rodent faecal virome.

• DOI: 10.1111/mec.16778
• 发表时间: 2023-09
• 期刊: Molecular ecology
• 影响因子: 4.9
• 作者: Raghwani J;Faust CL;François S;Nguyen D;Marsh K;Raulo A;Hill SC;Parag KV;Simmonds P;Knowles SCL;Pybus OG
• 通讯作者: Pybus OG