Analyzing the role of the retinoic acid-inducible gene I (RIG-I) in response to avian influenza virus infection using transgenic chicken models

家禽是全世界人口蛋白质的重要来源。然而，它面临着与可能导致高死亡率的呼吸道感染有关的重大限制。这包括禽流感病毒（AIVs），这取决于它们在鸡中的致病性，它们可能感染广泛的组织，导致全身感染。控制艾滋病毒感染的困难是由于抗原漂移导致流感大流行和在某些情况下人类感染的复发。虽然家禽感染艾滋病病毒可能导致高死亡率，但包括鸭在内的水禽是艾滋病病毒的储存库，它们似乎能很好地应对感染。众所周知，鸭对aiv的抗性与RIG-I的存在高度相关，RIG-I是一种细胞质RNA解旋酶，它与线粒体蛋白相互作用，以检测病毒RNA的存在并诱导IFN合成。鸭对aiv的抗性也可能与ring finger protein 135 （RNF135）有关，RNF135是一种rig - 1结合蛋白，负责rig - 1的激活。鸡基因组中不存在rig - 1和RNF135，这可能是鸡对不同亚型禽流感病毒具有较高易感性的原因。除了参与启动先天免疫应答外，最近的研究表明rig - 1在小鼠的进一步免疫过程中发挥作用，包括树突状细胞激活和T细胞启动。在鸡中没有发现类似的功能，因为到目前为止还没有产生表达RIG-I/RNF135的鸡。该项目旨在产生rig - 1 /RNF135转基因鸡，随后将用于分析这些基因在体内的功能。这将提供有关它们在禽类免疫系统中的作用的基本知识，并将有助于减少鸡对aiv的易感性。

Poultry represents an important source of protein for human populations worldwide. However, it is facing major constraints related to respiratory infections that may lead to high mortalities. This includes avian influenza viruses (AIVs), which depending on their pathogenicity in the chicken, they may infect a wide range of tissues leading to systemic infections. Difficulties in the control of AIV-infections are due to antigenic drift that causes the recurrence of influenza pandemics and in some cases human infections. While AIV-infection of domestic poultry may lead to high mortality, waterfowl including ducks represent a reservoir for AIVs and they seem to cope quite well with the infection. It is known that duck-resistance against AIVs is highly associated with the presence of RIG-I which is a cytoplasmic RNA helicase that interacts with mitochondrial proteins in order to detect the presence of viral RNA and induce IFN synthesis. It is also possible that duck-resistance against AIVs is related to the ring finger protein 135 (RNF135) which is a RIG-I binding protein responsible for RIG-I activation. RIG-I and RNF135 are absent in the chicken genome which could be responsible for higher susceptibility of this species to different AIV-subtypes. Other than being involved in priming the innate immune response, recent studies indicated the role of RIG-I in further immunological processes in mice including dendritic cell activation and T cell priming. No similar functions were identified in chickens since no RIG-I/RNF135 expressing chickens were generated so far. This project aims to generate RIG-I/RNF135 transgenic chickens that will be subsequently used to analyze the function of these genes in vivo. This will provide fundamental knowledge on their role in the avian immune system and will help reducing the susceptibility of chickens for AIVs.