[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众健康构成威胁。一些水鸟自然会感染禽流感病毒，例如鸭、鹅和天鹅，但这些病毒可能会传播到家禽种群中，从而造成经济破坏性后果。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 会使鸡的 IAV 感染恶化：研究发现 IBDV 会增加鸡群感染 IAV 的风险，导致鸡更长时间地排出 IAV，并降低 IAV 疫苗的有效性。总而言之，这些研究表明，来自水鸟的 IAV 将能够更容易地在先前接触过 IBDV 的鸡群中传播。然而，目前还没有研究IBDV如何影响家禽种群中IAV的传播和进化，也没有研究IBDV对水鸟种群中其他病毒感染传播的贡献。我们计划定义 IBDV 如何影响 IAV 潜伏期、禽类排出 IAV 的时间长短、排出 IAV 的量、感染前需要多少 IAV，以及未感染禽类在放置于环境中时被感染的可能性。感染组。然后，这些信息将被放入我们开发的数学模型中，以定义 IBDV 暴露对鸡群 IAV 爆发的影响。 IBDV 暴露也可能会改变 IAV 在鸡体内的进化方式，因此我们将确定感染后不同时间禽类中 IAV 排出的序列，以了解病毒随时间的变化情况。我们还获得了经过深入研究的水鸟种群，并且我们已经在该种群中发现了IBDV。我们储存了 2,000 多个来自这些鸟类的样本，我们计划用它们来确定有多少只鸟类接触过 IBDV（患病率）。我们还计划从更多种类的水鸟和较年轻的鸟类（更容易感染IBDV）中采集更多样本，以进一步研究这一问题。我们还计划确定在该种群中发现的 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 IBDV 传播的病毒数量和数量以及 IBDV 的存在是否存在相关性，来确定 IBDV 对水禽中禽病毒传播的贡献。该项目将产生的新信息将用于确定 IBDV 诱导的免疫抑制对 IAV 在鸡中的传播有多大影响，以及是否有助于病毒在水鸟中的传播。这可用于在另一次 IAV 爆发时影响基于政策的决策，以改善对该疾病的控制，例如通过改进 IBDV 监测和改进 IBDV 疫苗接种流程。此外，我们认为这可以应用于其他感染，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