Role of avian macrophages in the pathogenesis of infectious bronchitis virus infection

禽巨噬细胞在传染性支气管炎病毒感染发病机制中的作用

• 批准号: RGPIN-2016-04057
• 负责人: AbdulCareem, MohamedFaizal
• 金额: $ 2.04万
• 依托单位: University of Calgary
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2016
• 资助国家: 加拿大
• 起止时间: 2016-01-01 至 2017-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=614811
• 关键词: Role; avian; macrophages; pathogenesis; infectious

Poultry meat and eggs are important sources of protein in the Canadian diet. Canada’s poultry industry has been valued at ~ $3.9 billion (2014), contributing 6.9% of cash receipts to farming operations in Canada with annual production of 663 million birds and >7 billion eggs. However, a major limitation of the poultry industry is morbidity and mortality associated with viruses that enter via the respiratory mucosa. For example, infectious bronchitis (IB) is a highly contagious respiratory viral infection, with global impacts (including substantial effects on North American chickens) on health, productivity and costs. Control of IB is focused on vaccines containing laboratory-attenuated viruses, but there are frequently IB outbreaks in vaccinated chickens. There are two reasons for this. Firstly, weakened vaccine virus becomes pathogenic after passage through the flock. Secondly, mutation of field IB virus (IBV) (against the pressure imposed by vaccination) to more virulent forms causes severe disease. Consequently, a novel approach to mitigate effects of this disease is urgently required. Interactions between the host and IBV, as well as mechanisms that lead to either virus clearance or disease progression in chickens, are poorly understood. As a first step, new knowledge regarding the complexity of host-virus interactions, particularly host responses elicited against IBV, is required. To elucidate host-virus interactions, the initial focus will be on macrophages, cells known to have major roles in non-specific and specific host responses against viral infections in mammals. However, whether avian macrophages have roles in the disease progression of IB in chickens, as well as non-specific and specific host responses against IBV infection in chickens, has not been well characterized. Therefore, the roles of macrophages as well as the mediators produced by macrophages such as nitric oxide and interleukins in causing IB and/or conferring resistance against IB in chickens, will be studied. The proposed studies will produce new knowledge regarding interactions between the host and IBV, and mechanisms that lead to virus clearance or disease development in chickens. Given the paucity of current knowledge in this area, the proposed studies are expected to provide novel insights into the role of macrophages in host responses and disease progression of IBV infection in chickens. The long-term goal of the proposed research is to provide a basis for immune intervention strategies for the control of IBV infection, which is prevalent in Canada and globally causing significant economic losses in poultry industry.

禽肉和禽蛋是加拿大饮食中重要的蛋白质来源。加拿大家禽业的价值约为39亿美元(2014年)，占加拿大养殖业现金收入的6.9%，年生产6.63亿只家禽和70亿个鸡蛋。然而，家禽业的一个主要限制是与通过呼吸道粘膜进入的病毒相关的发病率和死亡率。例如，传染性支气管炎(IB)是一种高度传染性的呼吸道病毒感染，对健康、生产力和成本具有全球性影响(包括对北美鸡的重大影响)。对IB的控制主要集中在含有实验室减毒病毒的疫苗上，但在接种疫苗的鸡中经常爆发IB。造成这种情况的原因有两个。首先，弱毒疫苗病毒在通过鸡群后变得致病。其次，野毒株病毒(IBV)的变异(对抗疫苗接种施加的压力)变成更强的形式会导致严重的疾病。因此，迫切需要一种新的方法来减轻这种疾病的影响。宿主和IBV之间的相互作用，以及导致病毒清除或鸡疾病进展的机制，目前还知之甚少。作为第一步，需要关于宿主-病毒相互作用的复杂性的新知识，特别是引起对IBV的宿主反应。 为了阐明宿主与病毒的相互作用，最初的焦点将放在巨噬细胞上，巨噬细胞是已知在哺乳动物对病毒感染的非特异性和特异性宿主反应中发挥主要作用的细胞。然而，禽类巨噬细胞是否在鸡传染性支气管炎的发病过程中起作用，以及鸡对IBV感染的非特异性和特异性宿主反应还没有得到很好的表征。因此，将研究巨噬细胞以及巨噬细胞产生的介质，如一氧化氮和白介素类在引起鸡的IB和/或赋予对IB的抵抗力中的作用。 拟议的研究将产生关于宿主和IBV之间的相互作用以及导致病毒清除或鸡疾病发展的机制的新知识。鉴于目前在这一领域的知识匮乏，拟议的研究有望为巨噬细胞在宿主反应和鸡传染性支气管炎病毒感染的疾病进展中的作用提供新的见解。这项拟议研究的长期目标是为控制IBV感染的免疫干预策略提供基础。IBV感染在加拿大和全球范围内流行，给家禽养殖业造成了重大经济损失。