Avian influenza H7N9 virus evolution: defining the impact of internal genes on virus infection in avian and mammalian species

禽流感 H7N9 病毒进化：定义内部基因对禽类和哺乳动物病毒感染的影响

• 批准号: BB/N002571/1
• 负责人: Munir Iqbal
• 金额: $ 85.16万
• 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: 2016
• 资助国家: 英国
• 起止时间: 2016 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FN002571%2F1
• 关键词: Avian; influenza; H7N9; virus; evolution

In nature, many distinct subtypes of avian influenza (AI) viruses circulate in wild aquatic birds with no consequence to farmed poultry or human health. However, on occasion, these viruses infect domesticated poultry and undergo genetic changes that sometimes result in the emergence of novel viruses with unforeseen biological and pathological characteristics. In recent years, a number of novel AI viruses including H5N1, H5N2, H5N8, H7N1, H7N2, H7N3, H7N7, H7N9, H9N2 and H10N8 have emerged in poultry. H5N1 and H9N2 strains have, within a short space of time, spread to many countries globally, inflicting enormous economic losses together with zoonotic infections of humans with fatal outcomes. In 2013, a novel H7N9 AI virus strain emerged in poultry in China and caused a localized epidemic in humans. The virus is characterised as having a low pathogenicity phenotype and causes subclinical disease and no mortality in chickens. However, human contact with infected birds has led to sporadic severe disease in humans and over 180 fatalities. The virus is now enzootic in poultry in China and possibly other neighboring regions. In order to reduce its zoonotic impacts, large scale culling of infected and potential contact poultry flocks is being carried out in China, with losses so far amounting to over $6.5 billion and predicted to increase substantially. These pre-emptive control measures have become less effective as the spread of the virus in birds widens. The virus continues to evolve and new reassortant genotypes are emerging, carrying genes of other co-circulating poultry influenza virus strains. This exceptionally rapid evolution may potentially drive further increases in virus infectivity, transmissibility and virulence for both poultry and humans; posing great threats to global food security, animal and public health, socioeconomic wellbeing and the environment.Considering the emerging and potentially global consequences of this novel H7N9 virus, there is an urgent need to bring this virus under control, reduce its prevalence in the environment and halt its spread to humans. Developing such control measures requires a comprehensive knowledge base about the nature of infecting virus, such as the viral factors that allow cross-species infection, the rates and mechanism of transmission between birds and from birds to humans and the genetic determinants of virulence in mammalian species compared to birds. The proposed research aims to gain insight into the viral factors that are contributing to the emergence and spread of novel H7N9 virus within poultry, and its transmission to and pathogenicity in humans (using a well-characterised ferret model for human infection). We will also assess the potential threat presented by virus strains that could emerge by similar reassortment events in the future. This project will investigate: (i) how does the internal H9N2 gene cassette change the virological properties of H7N9 influenza virus?; (ii) how do internal gene cassettes from diversified clades of H9N2 viruses impact on H7N9 virus pathogenesis and transmission in avian and mammalian species?; and (iii) how do the H7N9 viruses transmits from poultry to humans?The linking of identified genetic signatures associated with cross-species transmission and virulence with publically available virus genetic data will ultimately help to better predict potential immediate threats. The knowledge gained during this study will enable the design and development of improved tailor-made tools including vaccines, diagnostic reagents and antivirals allowing better control and management of AI infections. Improved control measures together with offering direct benefits may also provide substantial indirect economic, public health, environmental and social benefits to wider communities on both the national and global scale.

在自然界中，禽流感病毒的许多独特亚型在野生水生鸟中循环，对养殖家禽或人类健康没有影响。但是，有时这些病毒感染了家禽并经历了遗传变化，有时会导致具有不可预见的生物学和病理特征的新型病毒的出现。近年来，包括H5N1，H5N2，H7N1，H7N2，H7N3，H7N3，H7N7，H7N7，H7N9，H9N2和H10N8在内的许多新型AI病毒已经出现在家禽中。 H5N1和H9N2菌株在很短的时间内就传播到了全球许多国家，造成了巨大的经济损失，以及人畜共患感染的人类感染致命的结果。 2013年，中国的家禽中出现了一种新型的H7N9 AI病毒菌株，并引起了人类的局部流行。该病毒的特征是致病性表型低，并引起亚临床疾病，并且没有死亡的鸡死亡。然而，人类与受感染的鸟类的接触导致人类零星的严重疾病和180多人死亡。现在，该病毒在中国及其他邻近地区的家禽中是Enzootic。为了减少人畜共患影响，中国正在大规模淘汰感染和潜在的接触家禽羊群，到目前为止损失超过65亿美元，预计将大幅增加。随着病毒在鸟类中的传播扩大，这些先发制人的控制措施变得越来越有效。该病毒继续进化，新的替代基因型正在出现，携带其他共同循环的家禽流感病毒菌株的基因。这种异常快速的进化可能会进一步推动家禽和人类的病毒感染性，可传播性和毒力的进一步增加。对全球粮食安全，动物和公共卫生，社会经济福祉和环境构成巨大威胁。考虑到这种新型H7N9病毒的新兴和潜在的全球后果，迫切需要将这种病毒控制在控制范围内，减少其环境的普遍性，并停止其蔓延到人类。制定这种控制措施需要有关感染病毒性质的全面知识基础，例如允许跨物种感染的病毒因素，与鸟类相比，哺乳动物物种中鸟类和从鸟类之间传播的速率和机制以及哺乳动物物种毒力的遗传决定因素。拟议的研究旨在深入了解造成家禽中新型H7N9病毒的出现和传播的病毒因素，以及其传播到人类中的传播和致病性（使用人类感染的特征良好的雪貂模型）。我们还将评估病毒菌株所带来的潜在威胁，这些威胁可能会因将来的类似重新分类事件而出现。该项目将研究：（i）内部H9N2基因盒如何改变H7N9流感病毒的病毒学特性？ （ii）来自H9N2病毒多元化进化枝的内部基因盒如何影响禽和哺乳动物物种的H7N9病毒发病机理和传播？ （iii）H7N9病毒如何从家禽传播到人类？与跨物种传播和毒力与公开可用病毒遗传数据相关的已鉴定遗传特征的联系将最终有助于更好地预测潜在的即时威胁。在这项研究中获得的知识将使改进的量身定制工具的设计和开发，包括疫苗，诊断试剂和抗病毒药，从而可以更好地控制和管理AI感染。改进的控制措施以及提供直接利益的措施还可能为国家和全球规模的更广泛社区提供大量间接的经济，公共卫生，环境和社会福利。

项目成果

First molecular characterisation of avian metapneumovirus (aMPV) in Turkish broiler flocks

土耳其肉鸡群中禽间质肺病毒 (aMPV) 的首次分子表征

• 发表时间: 2018
• 期刊: Avian Diseases
• 影响因子: 1.4
• 作者: Bayraktara E

Amino Acid Residue 217 in the Hemagglutinin Glycoprotein Is a Key Mediator of Avian Influenza H7N9 Virus Antigenicity.

• DOI: 10.1128/jvi.01627-18
• 发表时间: 2019-01-01
• 期刊: Journal of virology
• 影响因子: 5.4
• 作者: Chang P;Sealy JE;Sadeyen JR;Iqbal M
• 通讯作者: Iqbal M

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

Coinfection of Chickens with H9N2 and H7N9 Avian Influenza Viruses Leads to Emergence of Reassortant H9N9 Virus with Increased Fitness for Poultry and a Zoonotic Potential.

• DOI: 10.1128/jvi.01856-21
• 发表时间: 2022-03-09
• 期刊: Journal of virology
• 影响因子: 5.4
• 作者: Bhat S;James J;Sadeyen JR;Mahmood S;Everest HJ;Chang P;Walsh SK;Byrne AMP;Mollett B;Lean F;Sealy JE;Shelton H;Slomka MJ;Brookes SM;Iqbal M
• 通讯作者: Iqbal M

Replicative fitness and transmission of G57 lineage and UDL01 like H9N2 viruses in chickens

• DOI: 10.1099/acmi.ac2019.po0585
• 发表时间: 2019-01-01
• 期刊: ABSTR MICR SOC ANN C
• 作者: Bhat, S;Shelton, H;Iqbal, M.
• 通讯作者: Iqbal, M.