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

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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.