On January 8, 2014, researchers at JianfengDai’s group published an article entitled “Matrix Metalloproteinase 3 Promotes Cellular Anti-Dengue Virus Responsevia Interaction with Transcription Factor NFkB in Cell Nucleus” in Plos One.
Denguevirus (DENV), the causative agent of human Dengue hemorrhagic fever, is amosquito-borne virus of immense global health importance. Characterization ofcellular factors promoting or inhibiting DENV infection is important forunderstanding the mechanism of DENV infection. In this report, MMP3(stromelysin-1), a secretory endopeptidase that degrades extracellularmatrices, has been shown promoting cellular antiviral response against DENVinfection. Quantitative RT-PCR and Western Blot showed that the expression ofMMP3 was upregulated in DENV-infected RAW264.7 cells. The intracellular viralloads were significantly higher in MMP3 silenced cells compared with controls.The expression level of selective anti-viral cytokines were decreased in MMP3siRNA treated cells, and the transcription factor activity of NFkB wassignificantly impaired upon MMP3 silencing during DENV infection. Further, wefound that MMP3 moved to cell nucleus upon DENV infection and colocalized withNFkB P65 in nucleus. Co-immunoprecipitation analysis suggested that MMP3directly interacted with NFkB in nucleus during DENV infection and theC-terminal hemopexin-like domain of MMP3 was required for the interaction. Thisstudy suggested a novel role of MMP3 in nucleus during viral infection andprovided new evidence for MMPs in immunomodulation.
Xiangyang Zuo is the first authors of the paper. Contributingauthor are Wen Pan, Tingting Feng and Xiaohong Shi. Prof.Jianfeng Dai is the corresponding author of thepaper. This work was supported by a Project Funded by the PriorityAcademic Program Development of Jiangsu Higher Education Institutions (PAPD), Programfor Changjiang Scholars and Innovative Research Team in University (PCSIRT)(IRT1075), National Natural Science Foundation of China (NSFC) (81172812, 81271792,31200648) and Jiangsu Natural Science Foundation (BK2012180), J.D. is a memberof Jiangsu Provincial Innovative Research Team. The funders had no role instudy design, data collection and analysis, decision to publish, or preparationof the manuscript.