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

家禽是全世界人类蛋白质的重要来源。然而，它正面临着与可能导致高死亡率的呼吸道感染有关的重大制约因素。这包括禽流感病毒（AIV），根据其在鸡体内的致病性，它们可能感染广泛的组织，导致全身感染。在控制艾滋病毒感染方面的困难是由于抗原漂移造成流感大流行的复发，在某些情况下造成人类感染。虽然家禽的AIV感染可能导致高死亡率，但水禽（包括鸭）是AIV的储存库，它们似乎能很好地科普感染。已知鸭对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，其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的抗性也可能与环指蛋白135（RNF 135）有关，RNF 135是负责RIG-I活化的RIG-I结合蛋白。RIG-I和RNF 135在鸡基因组中缺失，这可能是该物种对不同AIV亚型的易感性较高的原因。除了参与引发先天免疫应答之外，最近的研究表明RIG-I在小鼠中的进一步免疫过程中的作用，包括树突状细胞活化和T细胞引发。在鸡中没有鉴定出类似的功能，因为迄今为止没有产生表达RIG-I/RNF 135的鸡。本项目的目的是获得RIG-1/RNF 135转基因鸡，随后将用于分析这些基因在体内的功能。这将提供有关其在禽类免疫系统中作用的基本知识，并将有助于降低鸡对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.