Immunogenetics of antiviral immunity in ducks

鸭抗病毒免疫的免疫遗传学

• 批准号: RGPIN-2015-05045
• 负责人: Magor, Katharine
• 金额: $ 3.28万
• 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: 2018
• 资助国家: 加拿大
• 起止时间: 2018-01-01 至 2019-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=658424
• 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. This would be useful to know for farming resistant ducks, as well as conservation efforts aimed at maintaining a healthy population of wild ducks in the ecosystem, and for hunting. 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 their exploitation as the host of most strains of influenza, while 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. 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 Natural Killer cells. We have blood samples from 50 wild mallard ducks and we have used these to examine diversity of the genes for MHC class I that allow presentation of viral peptides to cytotoxic T cells. Our data show that ducks have a lot of diversity in the population, but individuals use only one gene while humans use 3 genes. The proteins made by this one gene can present a much smaller number of viral proteins to enable detection. This is likely to limit the ability of ducks to see influenza infected cells, and contributes to why ducks are the host of influenza. One puzzle we are trying to understand is that the expression of these genes is too early for adaptive immunity. We know these proteins (in humans) are involved also in NK cell recognition and perhaps this is why they are expressed so early. NK cells are first responders to a viral infection. To know how NK cells in ducks work, we will identify NK cell receptors from our 50 ducks. Again we expect these to be different between individuals, and some may be better at controlling NK cell killing. Our research will contribute to understanding the ways in which influenza viruses exploit the duck as a host and reservoir. While we focus mainly on wild ducks, this work can inform breeding and selection of influenza-resistant ducks and conservation of natural populations in the wild.**

我的NSERC研究项目的重点是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，在加拿大的湖泊中，任何时候都有15-30%的野鸭感染了流感。我们想知道鸭子是如何清除病毒的，并能够将鸭子的遗传与它们的疾病易感性/抗性联系起来。了解这一点对于养殖抗药鸭，以及旨在维持生态系统中野鸭健康种群的保护工作，以及狩猎都很有用。清除病毒涉及免疫反应的三个方面；抗体、适应性免疫（包括杀死被感染细胞的白细胞）和先天免疫。我们认为，适应性免疫受损是它们作为大多数流感毒株宿主的原因，而先天免疫使它们能够在高致病性禽流感中存活。我们的长期目标是从免疫学角度了解这些宿主-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。控制宿主免疫反应的基因位于主要组织相容性复合体的一条染色体上。物种中这些基因的多样性决定了它们能否成功对抗病毒病原体。我们正在探索控制三种白细胞的基因多样性，辅助和细胞毒性T细胞和自然杀伤细胞。我们有50只野生绿头鸭的血液样本，我们用这些样本来检查MHC I类基因的多样性，MHC I类允许病毒肽向细胞毒性T细胞呈递。我们的数据显示，鸭子在种群中有很多多样性，但个体只使用一个基因，而人类使用3个基因。由这个基因产生的蛋白质可以呈现出数量少得多的病毒蛋白，从而使检测成为可能。这可能会限制鸭子看到流感感染细胞的能力，并有助于解释为什么鸭子是流感的宿主。我们试图理解的一个谜题是，这些基因的表达对于适应性免疫来说太早了。我们知道这些蛋白质（在人类中）也参与NK细胞识别，也许这就是为什么它们表达得如此之早。NK细胞是对病毒感染的第一反应者。为了了解NK细胞在鸭子体内的工作原理，我们将从50只鸭子中鉴定NK细胞受体。同样，我们预计这些在个体之间是不同的，有些人可能更擅长控制NK细胞的杀伤。我们的研究将有助于理解流感病毒利用鸭子作为宿主和宿主的方式。虽然我们主要关注野鸭，但这项工作可以为抗流感鸭的繁殖和选择以及野生自然种群的保护提供信息