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

家禽是世界各地人类的重要蛋白质来源。然而，它正面临与可能导致高死亡率的呼吸道感染有关的重大制约。这包括禽流感病毒(AIV)，根据其在鸡体内的致病性，它们可能会感染广泛的组织，导致全身感染。控制禽流感病毒感染的困难是由于抗原漂移导致流感大流行的复发，在某些情况下还会导致人类感染。虽然家禽感染禽流感病毒可能会导致高死亡率，但包括鸭子在内的水禽是禽流感病毒的蓄水池，它们似乎能够很好地应对感染。已知，鸭对禽流感病毒的抗性与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的存在并诱导干扰素的合成。鸭对禽流感的抗性也可能与环指蛋白135(RNF135)有关，RNF135是一种RIG-I结合蛋白，负责RIG-I的激活。RIG-I和RNF135在鸡基因组中缺失，这可能是该物种对不同AIV亚型具有较高易感性的原因。除了参与启动先天免疫反应外，最近的研究表明，Rig-I在小鼠进一步的免疫过程中发挥作用，包括树突状细胞激活和T细胞启动。由于到目前为止还没有RIG-I/RNF135的表达鸡，因此在鸡中没有发现类似的功能。该项目旨在培育RIG-I/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作用的基本知识，并有助于降低鸡对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.