miR146a facilitates DENV2 replication by targeting TRAF6 and inhibiting interferon production (168.19)
Xi Huanga b c d e f, Siyu Wub c e f, Ping Zhangb c e f
- aAnatomy and Cell Biology, Wayne State University School of Medicine , Detroit, MI
- bImmunology and Microbiology, Sun Yat-sen University , Guangzhou
- cInstitute of Human Virology, Sun Yat-sen University , Guangzhou
- d1Anatomy and Cell Biology, Wayne State University School of Medicine, Detroit, MI
- e2Immunology and Microbiology, Sun Yat-sen University, Guangzhou, China
- f3Institute of Human Virology, Sun Yat-sen University, Guangzhou, China
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Abstract
Abstract microRNAs (miRNAs) are involved in the regulation of multiple cellular processes and have recently been indicated to modulate the innate immune response. However, the role of miRNAs in dengue virus (DENV) infection remains unknown. Our study test the expression of several innate immune-related miRNAs, including miR-9, 21, 132, 146a and 155, in the monocytic cells after infection with DENV serotype 2 (DENV2). Among these miRNAs, miR-146a expression was significantly increased by DENV2 infection, and its induction was impaired by inhibition of IKK, NF-κB, p38 or JNK mitogen-activated protein kinase (MAPK), or by silencing of interferon-γ promoter stimulator 1 (IPS-1). In addition, our data revealed that miR-146a facilitated DENV2 replication, accompanied by a significantly downregulation of TNFR-associated factor 6 (TRAF6), interferons (IFNs), as well as IFN-stimulated genes. Finally, knockdown of TRAF6 enhanced the DENV2 replication and reduced the IFN production, while overexpression of TRAF6 successfully reversed the proviral effect mediated by miR-146a, suggesting that miR-146a exerts its functions through targeting TRAF6, thereby destroying the IFN and the antiviral state. These findings suggest that miR-146a might be a promising therapeutic target for dengue disease.
TL;DRFindings suggest that miR-146a might be a promising therapeutic target for dengue disease because it exerts its functions through targeting TRAF6, thereby destroying the IFN and the antiviral state. (Semantic Scholar)