Bilateral BBSRC-FAPESP Research Grant: Dissecting Essential Roles of Chicken Interferon Stimulated Genes in the Pathobiology of Poultry Viruses

BBSRC-FAPESP 双边研究资助：剖析鸡干扰素刺激基因在家禽病毒病理学中的重要作用

• 批准号: BB/M008681/2
• 负责人: Muhammad Munir
• 金额: $ 16.96万
• 依托单位: Lancaster University
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2018
• 资助国家: 英国
• 起止时间: 2018 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FM008681%2F2
• 关键词: Bilateral; BBSRC; FAPESP; Research; Grant

Poultry sectors of the UK and Brazil are contributing significantly to the cheapest and the most accessible source of meat protein. The UK poultry industry is contributing around £4 billion to the national economy whereas Brazil is the largest producer of poultry and poultry products, after United States and China. Despite this high production, infectious diseases are a major hurdle in achieving increasing demands of poultry products, around the globe. The total losses caused by infectious disease are enormous. For example, only Marek's disease virus (MDV), a cancer-causing virus of poultry, accounts for £2 billion losses worldwide. Massive vaccines application remained major disease-controlling tool against viruses. Despite widespread vaccinations against viruses (e.g. 22 billion vaccine doses for MDV only per year), the threat from poultry diseases is on rise and highlights the gaps in our fundamental understanding of poultry responses against virus natural infections or in immunization (vaccines). Such gaps has left us indebted on the molecular mechanism of chicken's involvement in influenza zoonoses and as a result quarantine and slaughtering of infected birds, as only choice, cost the poultry industry billions of dollars. Interferons, produced following viral infection of avian cells, stimulate the expression of hundreds of genes (more than 350 in humans) called interferon stimulated genes (ISGs). Exploitation of these ISGs could potentially be applied in favour of vaccine production, better vaccination protocols and controlling infections. In this proposal, we will initially identify the nature and magnitude of chicken ISGs (chISGs) and study their effects against five avian viruses causing infections in poultry (chicken, duck, turkey) ranging from mild to severe in terms of clinical manifestation. These viruses are of immense commercial and zoonotic importance not only for UK and Brazil but also throughout the world. Using broad-range profiling systems, we will identify those chISGs in the chicken cells that inhibit or enhance virus infections. Once identified, the factors that enhance virus infection will be overexpressed in established chicken cell line and the ones that inhibit virus infection will be removed or silenced within chicken cells. This modified cell line will be used to increase the replication of viruses for both industrial vaccine production and laboratory scale virus isolation. Given the fact that the current global poultry vaccine market is high, even a ten-fold increase in virus yield, which is potentially achievable, would have significant impact on the cost for vaccine. Beside industrial relevance, this new proposal, to be carried out jointly between The Pirbright Institute, UK and the State University of Campinas, Brazil, is crucial to understand the mechanism by which viruses induce interferon system of the chicken, some of which will be applicable to other species such as duck or turkeys. Finally, the findings from the project will be very valuable in examining the ability of the chISGs to protect the chickens against viruses of both poultry importance and those that can switch from poultry to human.

英国和巴西的家禽部门贡献了最便宜，最容易获得的肉蛋白来源。英国派利特行业为国民经济贡献了约40亿英镑，而巴西是美国和中国之后的最大的Poletry和Poletry产品生产国。尽管产量很高，但传染病还是在全球范围内实现Poletry产品需求不断增长的主要障碍。由传染病造成的总损失是巨大的。例如，仅Marek病毒病毒（MDV）是一种由癌症的家禽病毒，在全球范围内造成20亿英镑的损失。大量疫苗的应用仍然是针对病毒的主要疾病控制工具。尽管针对病毒的宽度疫苗（例如，每年只有220亿次疫苗剂量的疫苗剂量），但波利米疾病的威胁仍在上升，并强调了我们对针对病毒自然感染或免疫抑制（疫苗）的家禽反应的基本理解的差距。这样的差距使我们重视鸡肉参与流感人畜共患病的分子机制，因此隔离和被感染的鸟类屠杀，这是唯一的选择，损失了Polemy Industry Industry行业数十亿美元。在禽类细胞病毒感染后产生的干扰素刺激了称为干扰素刺激基因（ISGS）的数百个基因（超过350个）的表达。可能会使用这些ISG的剥削来实施疫苗生产，更好的疫苗方案和控制感染。在此提案中，我们最初将确定鸡肉ISG（Chisgs）的性质和幅度，并研究它们对五种禽病毒的作用，从而在临床表现方面从轻度到重度引起家禽（鸡肉，鸭，土耳其）感染。这些病毒不仅对英国和巴西，而且在世界范围内也具有巨大的商业和人畜共患关系。使用宽范围的分析系统，我们将识别鸡细胞中抑制或增强病毒感染的chisgs。一旦确定，增强病毒感染的因素将在既定的鸡细胞系中过表达，并且抑制病毒感染的因素将在鸡细胞中去除或沉默。这种修饰的细胞系将用于增加工业疫苗生产和实验室规模隔离病毒的复制。鉴于当前的全球家禽疫苗市场很高，甚至可能成功的病毒产量增加了十倍，这可能会对疫苗的成本产生重大影响。除工业相关性外，这项新提案将在英国皮尔布赖特研究所（Pirbright Institute）和巴西坎皮纳斯大学（State Campinas）之间共同执行，这对于了解病毒影响鸡的干扰系统的机制至关重要，其中一些病毒将适用于其他物种，例如其他物种，例如鸭子或火鸡。最后，该项目的发现对于检查奇斯（Chisgs）保护鸡免受家禽重要性病毒的能力以及可以从家禽转变为人类的病毒的能力将非常有价值。

项目成果

Structural and Virus Regulatory Insights Into Avian N6-Methyladenosine (m6A) Machinery

• DOI: 10.3389/fcell.2020.00543
• 发表时间: 2020-07-15
• 期刊: FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
• 影响因子: 5.5
• 作者: Bayoumi, Mahmoud;Rohaim, Mohammed A.;Munir, Muhammad
• 通讯作者: Munir, Muhammad

Fundamental Characteristics of Bat Interferon Systems.

• DOI: 10.3389/fcimb.2020.527921
• 发表时间: 2020
• 期刊: Frontiers in cellular and infection microbiology
• 影响因子: 5.7
• 作者: Clayton E;Munir M
• 通讯作者: Munir M

Genetic diversity of bats coronaviruses in the Atlantic Forest hotspot biome, Brazil.

• DOI: 10.1016/j.meegid.2016.07.034
• 发表时间: 2016-10
• 期刊: Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases
• 作者: Góes LGB;Campos ACA;Carvalho C;Ambar G;Queiroz LH;Cruz-Neto AP;Munir M;Durigon EL
• 通讯作者: Durigon EL

Structural Insights Into m6A-Erasers: A Step Toward Understanding Molecule Specificity and Potential Antiviral Targeting.

• DOI: 10.3389/fcell.2020.587108
• 发表时间: 2020
• 期刊: Frontiers in cell and developmental biology
• 影响因子: 5.5
• 作者: Bayoumi M;Munir M
• 通讯作者: Munir M

The Application of NHEJ-CRISPR/Cas9 and Cre-Lox System in the Generation of Bivalent Duck Enteritis Virus Vaccine against Avian Influenza Virus.

• DOI: 10.3390/v10020081
• 发表时间: 2018-02-13
• 期刊: Viruses
• 作者: Chang P;Yao Y;Tang N;Sadeyen JR;Sealy J;Clements A;Bhat S;Munir M;Bryant JE;Iqbal M
• 通讯作者: Iqbal M