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CNOT2 facilitates dengue virus infection via negatively modulating IFN-Independent Non-Canonical JAK/STAT pathway

Liu, Jianan, Yang, Li, Liu, Feifei, Li, Heng, Tang, Wei, Tong, Xiankun, Zuo, Jianping
Biochemical and biophysical research communications 2019 v.515 no.3 pp. 403-409
Dengue virus, RNA interference, RNA replication, dengue, enzymes, genes, innate immunity, messenger RNA, protein synthesis, public health
Dengue virus (DENV) infection is a public health problem worldwide. To establish infection in host cells, DENV require host cellular mechanism to suppress and evade innate immunity for their replication. In this study, Ccr4-Not complex genes were screened by using RNAi approach in DENV-infected A549 and Huh7 cells. We found that CNOT2 plays a proviral role in DENV infection. The expression level of CNOT2 was up-regulated in DENV-infected cells. Down-regulation of CNOT2 significantly reduced DENV RNA replication and protein synthesis. Mechanism study showed that CNOT2 knockdown enhanced JAK-STAT antiviral signaling during DENV infection. Further analysis revealed that CNOT2 negatively modulated IFN-Independent Non-Canonical JAK/STAT pathway by accelerating the mRNA decay of JAK1 and STAT1 via its interaction with CNOT6/6L and CNOT7/8 deadenylases. Overall, these results demonstrate that CNOT2 is a novel negative regulator of the JAK-STAT pathway and supports DENV infection.