FLU:Trailmap: Transmission and risk of avian influenza: learning more to advance preparedness

高致病性禽流感病毒（HPAIV）是全球动物健康的重大负担，并威胁着人类健康。自2020年以来，HPAIV入侵英国的情况显著增加，在2020年至2023年期间发现了350多个受感染的场所。野生鸟类种群也遭受了多种物种的大量死亡，随着海鸟感染的转变，英国鸟类首次出现了病毒感染的过度夏季。虽然病毒入侵仅限于H5N1亚型，但这些病毒交换遗传物质的能力意味着在英国已检测到超过12种不同的H5N1病毒。此外，感染压力的增加意味着该病毒已蔓延到清除性哺乳动物物种，自2020年以来在野生哺乳动物中检测到23例HPAIV。该项目是为了应对英国HPAIV感染检测的极端增加，分为五个工作包（wp），以提高我们对HPAIV的理解，帮助减轻入侵并改进未来预防策略的方法。工作包（WP1）将提高我们对农场生物安全实践的理解，确定现有障碍中的弱点，并确定如何实施有效的应对措施。通过详细调查和开展多部门访谈，将评估现有生物安全干预措施的依从性和有效性。产出将提供对有效性和实施挑战的见解，这将用于改善实地的生物安全。WP2将增进我们对促成这些病毒传播的因素的理解，包括了解野生鸟类网络之间以及与家禽之间的复杂相互作用。来自现场的病毒遗传和流行病学数据以及通过其他WPs生成的数据将被输入模型，从而提供对“高风险”活动的洞察。模拟种群及其相互作用将把WP1和WP5联系起来，以帮助了解现有和未来控制和缓解行动的有效性和影响。WP3将提高我们对野鸟和家禽中HPAIV传播动态的认识。通过对野生鸟类种群进行生物采样，我们将制定基于风险的监测计划，并在野生鸟类和家禽界面建立相互作用模型。这将有助于确定高风险入侵地点和可能在环境中持续传播的关键野生鸟类种群。产出将提供给WP2，使人们能够更好地了解潜在的感染宿主以及导致疾病从禽类宿主侵入家禽业的因素。WP4将评估导致不同疾病结果的病毒学因素。将评估病毒传染性和决定不同物种感染的因素。这将增强我们对病毒学相互作用的理解，并确定导致病毒出现的病毒因子的作用。该工作计划还将与其他工作计划的产出相联系，以检查驱动病毒多样性的机制和可能使病毒适应不同宿主的因素。最后，WP5将评估宿主因素（包括免疫）在控制易感性、结局、流行病学和病毒进化方面的作用。本项目将研究物种之间的分子差异如何影响疾病结果，并定义抗体对不同病毒蛋白的反应如何影响病毒出现的可能性，包括不同宿主之间的差异。我们将进一步研究在逃逸突变体出现中起重要作用的病毒结构域，以确定flex在宿主免疫反应靶向的病毒蛋白中存在的位置。我们还将评估实施疫苗接种可能对疫情产生的影响，从而为未来的缓解战略提供信息。

High pathogenicity avian influenza virus (HPAIV) is a significant burden on animal health globally and threatens human health. Incursions of HPAIV into the UK have increased significantly since 2020 with over 350 infected premises being detected between 2020 and 2023. Wild bird populations have also suffered significant mortalities across multiple species, with a shift to infection of seabirds enabling over-summering of virus infection in UK birds for the first time. Whilst virus incursions have been restricted to the H5N1 subtype, the ability of these viruses to exchange genetic material means that over 12 different H5N1 viruses have been detected in the UK. Further, the increased infection pressure has meant that the virus has spilt over into scavenging mammalian species with 23 detections of HPAIV in wild mammals since 2020. This project is in response to this extreme increase in detection of HPAIV infection in the UK and is divided across five work packages (WPs) to improve our understanding of HPAIVs, help mitigate incursions and refine approaches to future prevention strategies. Work-package (WP1) will improve our understanding of on-farm biosecurity practices, to define weaknesses in existing barriers and determine how to implement effective counter measures. Through detailed investigation and by conducting multi-sectorial interviews, the adherence and effectiveness of existing biosecurity interventions will be assessed. Outputs will provide insight into effectiveness and challenges to implementation which will be used to improve biosecurity in the field.WP2 will improve our understanding of factors which contribute to the circulation of these viruses, including understanding the complex interactions amongst wild bird networks and with poultry. Viral genetic and epidemiological data from the field, and data generated through the other WPs, will be input into models that will provide insight into 'high-risk' activities. Modelling populations and their interactions will link WP1 and WP5 to help understand the effectiveness and impact of existing and future control and mitigation actions.WP3 will improve our understanding of HPAIV transmission dynamics in both wild birds and poultry. By undertaking biological sampling across wild bird populations, we will develop risk-based surveillance programmes and model interactions at wild bird and poultry interfaces. This will enable a definition of high-risk incursion sites and critical wild bird populations responsible for potential sustained transmission within the environment. Outputs will feed into WP2 and enable a greater understanding of the potential reservoirs of infection as well as factors that drive incursion of disease from bird reservoirs into the poultry sector.WP4 will assess virological factors that drive differential disease outcomes. Both viral infectivity and factors that dictate infection of different species will be assessed. This will enhance our understanding of virological interactions and define the role of viral factors that contribute to viral emergence. This WP will also link to outputs from other WPs to examine the mechanisms that drive viral diversity and factors that may enable adaptation to different hosts.Finally, WP5 will assess the role of host factors, including immunity, in governing susceptibility, outcome, epidemiology, and virus evolution. This WP will investigate how molecular differences between species contribute to disease outcomes and define how antibody responses to different virus proteins impact upon the potential of virus emergence including variations across different hosts. Viral domains that are identified as being important in the emergence of escape mutants will be further investigated to define where flex exists within viral proteins targeted by the host immune response. We will also assess how the implementation of vaccination might impact on outbreaks and hence will inform future mitigation strategies.