[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.

由流感病毒（IAV）引起的“鸟流感”是对家禽行业和公共卫生生产力的威胁。一些水鸟自然被IAV感染，例如鸭，鹅和天鹅，但是病毒可以跳入家禽种群，并具有经济上的毁灭性后果。感染性囊肿病毒（IBDV）是一种可能破坏鸟类免疫系统的感染，导致所谓的免疫抑制。 IBDV可能会使鸡的IAV感染恶化：发现IBDV会增加鸡群IAV的风险，从而导致鸟类脱落IAV更长的时间，并降低IAV疫苗的有效性。综上所述，这些研究表明，来自水鸟的IAV将能够在以前暴露于IBDV的鸡群中更容易地传输。但是，尚未研究IBDV如何影响家禽种群的IAV传播和进化，或者IBDV对水鸟种群中其他病毒感染的传播所做的贡献。我们计划定义IBDV如何影响IAV孵育周期，时间鸟的长度，它们脱落的IAV量，被感染前需要多少IAV以及未感染的鸟类被置于感染组中时受到感染的可能性。然后将这些信息放入我们已经开发的数学模型中，以定义IBDV暴露对鸡群IAV爆发的影响。 IBDV的暴露也可能会改变鸡肉中IAV的演变方式，因此我们将在感染后不同时间从鸟类中脱落的IAV序列，以了解病毒随时间的变化。我们还可以进入经过深入研究的水鸟人群，并且我们已经在该人群中确定了IBDV。我们有2,000多个存储的样本，我们计划使用这些样本来确定有多少鸟暴露于IBDV（患病率）。我们还计划从各种各样的水鸟和幼鸟（更容易受到IBDV易受的）中采集更多样品，以进一步研究。我们还计划确定IBDV在该人群中识别的程度导致疾病以及它对鸟类免疫系统的破坏性。我们还将通过确定与病毒散开的数量和数量和IBDV的存在相关性来确定IBDV对鸟类病毒在水鸟中的扩散的贡献。该项目将生成的新信息将用于定义IBDV诱导的免疫抑制作用有多少有助于IAV在鸡中的传播以及它是否有助于病毒在水鸟中的传播。这可以用来影响基于政策的决策，以改善对疾病的控制，例如，通过改善IBDV的监视并改善IBDV疫苗接种过程。此外，我们认为这可以应用于其他感染，并且免疫系统的疾病可能会影响许多病毒在野生动植物和家畜中的传播和进化。

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.

Towards an understanding of the avian virome.

• DOI: 10.1099/jgv.0.001447
• 发表时间: 2020-08
• 期刊: The Journal of general virology
• 作者: François S;Pybus OG
• 通讯作者: Pybus OG