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

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 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 antiviral signaling during DENV infection. Further analysis revealed that CNOT2 negatively modulated IFN-Independent Non-Canonical pathway by accelerating the mRNA decay of JAK1 and via its interaction with CNOT6/6L and CNOT7/8 deadenylases. Overall, these results demonstrate that CNOT2 is a novel negative regulator of the JAK-duanyu1813 pathway and supports DENV infection.

KEYWORDS: {{ getKeywords(articleDetailText.words) }}