YY-EEID US-UK Collab: Combined influence of imperfect vaccines, host genetics, and non-genetic drivers on virus transmission and virulence evolution

YY-EEID 美英合作：不完善的疫苗、宿主遗传学和非遗传驱动因素对病毒传播和毒力进化的综合影响

• 批准号: BB/V017411/1
• 负责人: Andrea Doeschl-Wilson
• 金额: $ 207.74万
• 依托单位: University of Edinburgh
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2021
• 资助国家: 英国
• 起止时间: 2021 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FV017411%2F1
• 关键词: YY; EEID; US; UK; Collab

Summary (up to 4000 characters)To maintain human and animal health, it is extremely important to understand how pathogens like viruses are transmitted and evolve to higher virulence. It is this knowledge that enables employment of effective and sustainable control strategies. Thus, it is necessary to collect, assemble, and analyse highly accurate datasets to determine the short- and long-term effectiveness of disease control approaches, that include biosecurity, genetic selection for disease resistance, and widespread vaccination. In this project, an international, interdisciplinary team investigates the impact of these approaches on the spread and evolution of two avian pathogenic viruses - Marek's disease virus (MDV) and infectious bronchitis virus (IBV) - both of which are primarily controlled by imperfect vaccines. It has been argued that imperfect vaccines like those to MDV and IBV, or host genetic resistance may alter the balance of selection between pathogen transmission and virulence by allowing a few more divergent but still virulent strains to be transmitted at reduced cost. However, these hypotheses have not been proven, and predictive frameworks are lacking for determining the combined influence of host and viral genetics, as well as vaccination on viral transmission and evolution to increased virulence. To address these knowledge gaps, a series of transmission experiments have been designed that utilize unique resources and data from 7,000+ birds under highly controlled conditions. In summary, the primary goal of this research is to collect informative, high-resolution empirical data and use these to build the next generation of data-informed mathematical models of virus transmission and evolutionary dynamics as a function of vaccination status, host genetics, and/or viral mutation rates. We will also address the important and possibly interdependent questions of genome variability and evolution towards increased virulence in vivo.Besides the pure scientific merit of this research, we also strive towards lifting the project to high practical relevance. This requires a whole systems approach that also considers the broader socio-economic and political drivers of disease spread and virulence evolution. We will combine socio-economic studies with mathematical modelling to identify strategies for mitigating MD spread and MDV virulence evolution in sub-Saharan Africa, where poultry production is currently undergoing drastic increases in commercial production, similar to what was observed in the US in the 1960s.We propose the following objectives to achieve scientific excellence and attain broader impact:1. Determine the influence of imperfect vaccines, host genetics, and viral mutation rate on transmission and evolution to higher virulence.2. Validate viral genome polymorphisms associated with increased virulence and the ability of the virus to escape immune surveillance.3. Build data-informed evolutionary-epidemiological simulation models to develop strategies to control the ecology, evolution and economic burden of MD.4. Disseminate information on MDV and IBV, and the impact of vaccination to poultry producers and the public through training, workshops, online videos, seminars, and various engagement activities

摘要（最多4000个字符）为了维护人类和动物的健康，了解病毒等病原体如何传播并进化到更高的毒力非常重要。正是这种知识，使就业的有效和可持续的控制策略。因此，有必要收集、汇编和分析高度准确的数据集，以确定疾病控制方法的短期和长期有效性，包括生物安全、抗病基因选择和广泛接种疫苗。在该项目中，一个国际跨学科小组调查了这些方法对两种禽类致病性病毒-马立克氏病病毒（MDV）和传染性支气管炎病毒（IBV）-传播和进化的影响，这两种病毒主要由不完善的疫苗控制。有人认为，不完善的疫苗，如MDV和IBV的疫苗，或宿主遗传抗性，可能会改变病原体传播和毒力之间的选择平衡，使一些不同的，但仍然有毒的菌株以较低的成本传播。然而，这些假设尚未得到证实，缺乏预测框架来确定宿主和病毒遗传学的综合影响，以及疫苗接种对病毒传播和进化的影响。为了解决这些知识差距，设计了一系列传播实验，这些实验在高度控制的条件下利用了来自7,000多只鸟类的独特资源和数据。总之，本研究的主要目标是收集信息丰富的高分辨率经验数据，并利用这些数据建立下一代病毒传播和进化动力学的数据知情数学模型，作为疫苗接种状态，宿主遗传学和/或病毒突变率的函数。我们还将解决重要的和可能相互依赖的问题，基因组变异和进化，以增加体内毒力。除了纯科学价值的这项研究，我们还努力提高该项目的高度实际意义。这需要采取一种全系统的办法，同时考虑到疾病传播和毒力演变的更广泛的社会经济和政治驱动因素。我们将联合收割机的社会经济研究与数学模型相结合，以确定在撒哈拉以南非洲地区减缓MD传播和MDV毒力进化的策略，该地区的家禽生产目前正在经历商业生产的急剧增长，类似于20世纪60年代在美国观察到的情况。确定不完善的疫苗，宿主遗传学和病毒突变率对传播和进化到更高毒力的影响。HIV病毒基因组多态性与病毒毒力增加和逃避免疫监视的能力相关.建立基于数据的进化流行病学模拟模型，以制定控制MD.4的生态，进化和经济负担的策略。通过培训、工作坊、网上视频、研讨会和各种参与活动，向家禽生产商和公众传播有关MDV和IBV的信息，以及疫苗接种的影响

项目成果

Review: Livestock disease resilience: from individual to herd level.

• DOI: 10.1016/j.animal.2021.100286
• 发表时间: 2021-12
• 期刊: Animal : an international journal of animal bioscience
• 作者: Doeschl-Wilson A;Knap PW;Opriessnig T;More SJ
• 通讯作者: More SJ

Exploring the value of genomic predictions to simultaneously improve production potential and resilience of farmed animals.

• DOI: 10.3389/fgene.2023.1127530
• 发表时间: 2023
• 期刊: FRONTIERS IN GENETICS
• 影响因子: 3.7
• 作者: Zefreh, Masoud Ghaderi;Doeschl-Wilson, Andrea B.;Riggio, Valentina;Matika, Oswald;Pong-Wong, Ricardo
• 通讯作者: Pong-Wong, Ricardo

Impact of vaccination and selective breeding on the transmission of Infectious salmon anemia virus

• DOI: 10.1016/j.aquaculture.2021.736365
• 发表时间: 2021-03-30
• 期刊: AQUACULTURE
• 影响因子: 4.5
• 作者: Chase-Topping, Margo E.;Pooley, Chris;Doeschl-Wilson, Andrea
• 通讯作者: Doeschl-Wilson, Andrea

294. Selection for robustness: exploring the value of genomic prediction, reaction norm models and phenotyping strategies

294.稳健性选择：探索基因组预测、反应规范模型和表型策略的价值

• DOI: 10.3920/978-90-8686-940-4_294
• 发表时间: 2022
• 作者: Ghaderi-Zefreh M

Investigation of Gene Evolution and Phylodynamics in Marek's Disease Virus

马立克氏病病毒基因进化和系统动力学研究

• DOI: 10.2139/ssrn.4655021
• 发表时间: 2023
• 期刊: SSRN Electronic Journal
• 作者: Osterrieder N