NDR2 promotes the antiviral immune response via facilitating TRIM25-mediated RIG-I activation in macrophages.

ABSTRACT: 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

SUBMITTER: Liu Z 

PROVIDER: S-EPMC6365120 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature