Abstract:Human respiratory syncytial virus (hRSV) is the second leading aetiology of lower respiratory infection deaths in the world. Disease animal models play an important role in the development of vaccine and therapeutic drugs, and a variety of animals, including non-human primates such as chimpanzees, have been made to develop models of hRSV infection. However, the limitations such as semi-permissiveness and short duration of infection have impeded their applications in both the pathogenesis of hRSV and therapeutics development. Here, we presented an hRSV infection model based on IL2rg gene deficient rat using TALEN technology. IL2rg-/- knockout rats can sustain high viral loads in nasal cavity upon intranasal inoculation with hRSV. The average peak titer rapidly reached 1?010 copies/g in nasal tissue, as well as 1?07 copies/g up to 5 weeks post infection. Since IL2rg-/- knockout rats is genetically heritable, with stable traits and easy production, which facilitate the standardization of disease models. Compared with mice, rats have the advantages of being larger and more convenient for collecting sufficient samples. This IL2rg-/- rat model can be used to study the transmission and pathogenesis of hRSV and is a useful tool for evaluating therapies.