Abstract: Objective To overcome the limitations of existing human respiratory syncytial virus ( hRSV) animal models, such as semi-permissiveness and short duration of infection, this study established an IL2rg gene knockout (IL2rg- / -) rat model using TALEN gene editing technology. Methods The animal model was infected with hRSV intranasally. Clinical characteristics, body weight, and temperature changes were observed over the infection period(0 ~35 days). The total viral loads in respiratory organs, such as the nasal tissue, trachea, and lungs, were measured at various time points (4, 11, 20, and 35 days post-infection). Pathological analysis was conducted on target organs at the endpoint of observation ( 35 days post-infection). Changes in peripheral blood T, B, NK, and NKT cells and various cytokines were assessed at various time points(4, 20, and 35 days post-infection). Results (1) IL2rg- / - knockout rats sustained high viral loads in the nasal cavity upon intranasal inoculation with hRSV. The average peak titer rapidly reached 1 × 1010 copies/ g in nasal tissue and 1 × 107 copies/ g up to 5 weeks post-infection. ( 2) However, no significant pathological changes were noted in nasal, tracheal, or lung tissues. ( 3) An increase was observed in the content of peripheral blood B cells in hRSV-infected IL2rg - / - rats. (4) IL-6 and MCP-1 were increased in the early stage of infection and then decreased at the end of the observation period. Conclusions This study established a new IL2rg - / -rat model using TALEN technology and found that this model effectively supported high-level replication and long-term infection of hRSV, providing a good basis for antiviral drug screening and in vivo efficacy evaluation of anti-hRSV antibodies.
