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

Jianan Liu; Li Yang; Feifei Liu; Heng Li; Wei Tang; Xiankun Tong; Jianping Zuo

doi:10.1016/j.bbrc.2019.05.083

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

Biochem Biophys Res Commun. 2019 Jul 30;515(3):403-409. doi: 10.1016/j.bbrc.2019.05.083. Epub 2019 May 31.

Authors

Jianan Liu¹, Li Yang², Feifei Liu³, Heng Li⁴, Wei Tang⁵, Xiankun Tong⁶, Jianping Zuo⁷

Affiliations

¹ Laboratory 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. Electronic address: liujianan@simm.ac.cn.
² Laboratory of Immunopharmacology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China. Electronic address: yangli@simm.ac.cn.
³ Laboratory of Immunopharmacology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China. Electronic address: liufeifei@simm.ac.cn.
⁴ Laboratory of Immunopharmacology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China. Electronic address: s18-liheng@simm.ac.cn.
⁵ Laboratory of Immunopharmacology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China. Electronic address: tangwei@simm.ac.cn.
⁶ Laboratory of Immunopharmacology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China. Electronic address: xktong@simm.ac.cn.
⁷ Laboratory 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; Laboratory of Immunology and Virology, Shanghai University of Traditional Chinese Medicine, Shanghai, China. Electronic address: jpzuo@simm.ac.cn.

PMID: 31155293
DOI: 10.1016/j.bbrc.2019.05.083

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.

Keywords: CNOT2; Dengue virus; IFN; ISGs; JAK-STAT pathway.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cell Line, Tumor
Dengue / metabolism*
Dengue / virology*
Dengue Virus / metabolism*
Gene Knockdown Techniques
Humans
Interferons / metabolism*
Janus Kinases / metabolism*
RNA Stability / genetics
RNA, Messenger / genetics
RNA, Messenger / metabolism
Repressor Proteins / metabolism*
STAT Transcription Factors / metabolism*
Signal Transduction*

Substances

CNOT2 protein, human
RNA, Messenger
Repressor Proteins
STAT Transcription Factors
Interferons
Janus Kinases