Immunogenetics of antiviral immunity in ducks

鸭抗病毒免疫的免疫遗传学

• 批准号: RGPIN-2020-04668
• 负责人: Magor, Katharine
• 金额: $ 3.64万
• 依托单位: University of Alberta
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=744787
• 关键词: Immunogenetics; antiviral; immunity; ducks

My NSERC research program is focused on the immunogenetics of the wild duck population and its influence on their role as host of influenza. We know that 15-30% of wild ducks are infected with influenza in Canadian lakes at any time. We would like to know how ducks clear the virus, and be able to correlate the genetics of ducks with their disease susceptibility/resistance. We think ducks with one unique type of gene are better at flu defense, and we will test that hypothesis by sampling blood and flu infection status of wild ducks in Alberta. Alberta is the convergence of several North American flyways, so is ideal for flu surveillance. This would be useful to know for duck farming, as well as conservation efforts aimed at maintaining a healthy population of wild ducks in the ecosystem. Three arms of the immune response are involved in clearing viruses; antibodies, adaptive immunity involving white blood cells that kill infected cells, and innate immunity. We believe that impaired adaptive immunity is responsible for the duck's exploitation as the host of most strains of influenza, while robust innate immunity allows them to survive highly pathogenic avian influenza. Our long-term goal is to understand these host-pathogen interactions from an immunology perspective, and understand the role of genetic diversity in host immune responses. Research goals focus on investigating gene order, diversity and expression in the MHC region of the genome. The genes that control the host immune response are located on one chromosome in the Major Histocompatibility Complex. The diversity of these genes in the species determines their success against viral pathogens. We are exploring the diversity of genes that control three kinds of white blood cells, the helper and cytotoxic T cells and the B cells that make antibodies. Different MHC genotypes have different immune responses to virus and to vaccines. We are also exploring other MHC-linked genes, called TRIM genes, which upregulate innate immune responses. Stronger innate responses are instructive for overall better immune responses. Antibody repertoire analyses of wild ducks may provide insight into generation of broadly neutralizing anti-influenza antibodies (the holy grail for influenza vaccines) and from experimental infections, therapeutics to combat highly pathogenic avian influenza. Here we examine the diversity and function of genes involved in controlling the duck immune response; 1) MHC class I that presents viral peptides to cytotoxic T cells, 2) MHC class II that presents particles taken up by macrophages and presented to helper T cells. Helper T cells turn on cytotoxic T cells and B cells that make antibodies; and 3) the MHC-linked TRIM27-L protein that turns up the innate immune response. Understanding the diversity of genes involved in defense against influenza in the reservoir host may help us understand selective forces driving evolution of influenza strains circulating in the environment.

我的NSERC研究项目主要集中在野鸭种群的免疫遗传学及其对它们作为流感宿主的作用的影响。我们知道，加拿大湖泊中随时都有15-30%的野鸭感染流感。我们想知道鸭子是如何清除病毒的，并能够将鸭子的遗传学与它们的疾病易感性/抵抗力联系起来。我们认为具有一种独特基因的鸭子更善于防御流感，我们将通过对阿尔伯塔野鸭的血液和流感感染状况进行采样来验证这一假设。阿尔伯塔是北美几条飞行路线的交汇点，因此是流感监测的理想地点。这对于养鸭业以及旨在维持生态系统中野鸭健康种群的保护工作都是有用的。 免疫反应的三个分支涉及清除病毒;抗体，涉及杀死感染细胞的白色血细胞的适应性免疫，以及先天免疫。我们认为，受损的适应性免疫是鸭作为大多数流感病毒株宿主的原因，而强大的先天免疫使它们能够在高致病性禽流感中生存下来。我们的长期目标是从免疫学的角度了解这些宿主-病原体相互作用，并了解遗传多样性在宿主免疫反应中的作用。研究目标集中在调查基因组的MHC区域的基因顺序，多样性和表达。控制宿主免疫反应的基因位于主要组织相容性复合体中的一条染色体上。这些基因在物种中的多样性决定了它们对病毒病原体的成功。我们正在探索控制三种白色血细胞的基因的多样性，这三种血细胞是辅助性和细胞毒性T细胞以及制造抗体的B细胞。不同的MHC基因型对病毒和疫苗具有不同的免疫应答。我们还在探索其他与MHC相关的基因，称为TRIM基因，它可以上调先天免疫反应。更强的先天反应对于整体更好的免疫反应是有益的。野鸭的抗体库分析可以提供对产生广泛中和的抗流感抗体（流感疫苗的圣杯）和从实验感染，治疗，以打击高致病性禽流感的洞察。在这里，我们研究了参与控制鸭免疫反应的基因的多样性和功能; 1）MHC I类，将病毒肽呈递给细胞毒性T细胞，2）MHC II类，将巨噬细胞摄取的颗粒呈递给辅助T细胞。辅助性T细胞开启细胞毒性T细胞和产生抗体的B细胞; 3）MHC连接的TRIM 27-L蛋白，其开启先天免疫应答。了解宿主中参与防御流感的基因的多样性可能有助于我们了解驱动环境中流行的流感毒株进化的选择性力量。