Protective Role of LGP2 in Influenza Virus Pathogenesis

Influenza A virus triggers a contagious respiratory disease that can cause considerable morbidity and mortality. Using an in vitro approach, we previously demonstrated that the pattern recognition receptor retinoic acid– inducible gene I (RIG-I) plays a key role in influenza A virus–mediated immune response. However, the importance of RIG-I signaling in vivo has not been thoroughly examined, because of the lack of an appropriate mouse models. To circumvent this issue, we generated a new transgenic mouse overexpressing LGP2 (hereafter, “LGP2 TG mice”),a major regulatorof the RIG-I signalingpathway. The time course ofseveral parameters wascompared in infected wild-type and LGP2 TG mice. We found that LGP2 TG mice displayed significantly reduced inflammatory mediators and a lower leukocyte infiltration into the bronchoalveolar airspace. More importantly, LGP2 TGmicehad a significant survival advantage.Hence,our invivo studyrevealsthat LGP2 isa major downregulator of the influenza A virus–triggered detrimental inflammatory response.