Small interfering RNA expression inhibits avian infectious bronchitis virus replication and inflammatory response.

Yu, Kun; Deng, Shoulong; Wang, Hai; Zhang, Yi; Chen, Xuehui; Wang, Kejun; Hu, Rui; Lian, Zhengxing; Li, Ning

BACKGROUND Avian infectious bronchitis virus (IBV) is a major cause of poor weight gain and mortality among chicks. METHODS A lentivirus vector was used to generate transgenic chickens expressing small interfering RNA (siRNA) targeting the M protein of IBV. Offspring of generation 0 (G0) were screened to identify G1 transgenic chickens (Tg). Monocytes from G1 Tg were stimulated with IBV in vitro. RESULTS Monocytes producing siRNA efficiently inhibit IBV replication. Expression of inflammatory cytokines, Mx protein and nitric oxide levels were lower in early IBV infection in Tg. In vivo experiments show that siRNA expression inhibits IBV replication, significantly decreases mortality and increases weight gain. Inflammatory responses and oxidative damage were significantly decreased, yielding minimal tissue injury. The inflammatory responses indicate that the cellular immune response is most effective during the initial stage, while the humoral immune response is more significant in later stages of infection. CONCLUSIONS Small interfering RNA expression inhibits avian IBV replication and inflammatory response.