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Measuring Dengue Virus RNA in the Culture Supernatant of Infected Cells by Real-time Quantitative Polymerase Chain Reaction
Published on: November 1, 2018
CNOT2 facilitates dengue virus infection via negatively modulating IFN-Independent Non-Canonical JAK/STAT pathway
Jianan Liu1, Li Yang2, Feifei Liu2
1Laboratory of Immunopharmacology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China; University of Chinese Academy of Sciences, No.19A Yuquan Road, Beijing, 100049, China.
Abstract:
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.
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