| First Author | Liu Z | Year | 2019 |
| Journal | Sci Adv | Volume | 5 |
| Issue | 2 | Pages | eaav0163 |
| PubMed ID | 30775439 | Mgi Jnum | J:288793 |
| Mgi Id | MGI:6430088 | Doi | 10.1126/sciadv.aav0163 |
| Citation | Liu Z, et al. (2019) NDR2 promotes the antiviral immune response via facilitating TRIM25-mediated RIG-I activation in macrophages. Sci Adv 5(2):eaav0163 |
| abstractText | Retinoic acid-inducible gene I (RIG-I), a pivotal cytosolic sensor, recognizes viral RNAs to initiate antiviral innate immunity. However, posttranslational regulation of RIG-I signaling is not well understood. We report here that nuclear Dbf2-related kinase 2 (NDR2) functions as a crucial positive regulator of the RIG-I-mediated antiviral immune response. Overexpression of NDR2 or its kinase-inactive mutants potentiates RNA virus-induced production of type I interferons and proinflammatory cytokines and dampens viral replication. NDR2 conditional knockout mice (Lysm(+)NDR2(f/f)) show an impaired antiviral immune response. Mechanistically, NDR2 directly associates with RIG-I and TRIM25, thus facilitating the RIG-I/TRIM25 complex and enhancing the TRIM25-mediated K63-linked polyubiquitination of RIG-I, which is required for the RIG-I-mediated antiviral immune response. Furthermore, NDR2 expression is notably down-regulated in peripheral blood from respiratory syncytial virus-infected patients and in virus-infected macrophages. Collectively, these findings provide insights into the function of NDR2 in antiviral immunity and its related clinical significance. |
