RIG-I Signaling via MAVS Is Dispensable for Survival in Lethal Influenza Infection In Vivo.
Wenxin WuXiaoqiu WangWei ZhangLili TianJ Leland BoothElizabeth S DugganSunil MoreLin LiuMikhail DozmorovJordan P MetcalfPublished in: Mediators of inflammation (2018)
Retinoic acid-inducible gene I (RIG-I) is an important regulator of virus-induced antiviral interferons (IFNs) and proinflammatory cytokines. It requires interaction with an adaptor molecule, mitochondrial antiviral-signaling protein (MAVS), to activate downstream signaling pathways. To elucidate the mechanism(s) by which RIG-I-dependent recognition of IAV infection in vivo triggers innate immune responses, we infected mutant mice lacking RIG-I or MAVS with influenza A virus (IAV) and measured their innate immune responses. As has previously been demonstrated with isolated deletion of the virus recognition receptors TLR3, TLR7, and NOD2, RIG-I or MAVS knockout (KO) did not result in higher mortality and did not reduce IAV-induced cytokine responses in mice. Infected RIG-I KO animals displayed similar lung inflammation profiles as did WT mice, in terms of the protein concentration, total cell count, and inflammatory cell composition in the bronchoalveolar lavage fluid. RNA-Seq results demonstrated that all types of mice exhibited equivalent antiviral and inflammatory gene responses following IAV infection. Together, the results indicated that although RIG-I is important in innate cytokine responses in vitro, individual deletion of the genes encoding RIG-I or MAVS did not change survival or innate responses in vivo after IAV infection in mice.
Keyphrases
- immune response
- single cell
- high fat diet induced
- rna seq
- oxidative stress
- toll like receptor
- wild type
- dendritic cells
- inflammatory response
- genome wide
- signaling pathway
- diabetic rats
- coronary artery disease
- cardiovascular disease
- cell therapy
- genome wide identification
- copy number
- type diabetes
- gene expression
- nuclear factor
- cardiovascular events
- cell proliferation
- mesenchymal stem cells
- metabolic syndrome
- endothelial cells
- risk factors
- protein protein
- epithelial mesenchymal transition
- pi k akt
- small molecule
- skeletal muscle