Dengue Virus Targets the Adaptor Protein MITA to Subvert Host Innate Immunity

Yu, C. Y., T. H. Chang, et al. (2012) PLoS Pathog. 8(6):e1002780.

Speaker：Chan- Yi Su (蘇展儀)                                   Time：13:10~14:00 Sep. 19, 2012

Commentator：Dr. Yee-Shin Lin (林以行老師)          Place: Room 601

Abstract

Dengue virus (DENV) is the causative agent of the most prevalent arthropod-borne human viral disease, thus representing a significant global health burden. It is believed that type I interferons (IFNs) play important roles in host innate defense against DENV infection. To survive and replicate in host cells, DENV needs to evolve a way to downregulate the cellular IFN system. In this study, the author found that activation of interferon regulatory factor (IRF3) triggered by viral infection and by foreign DNA and RNA stimulation was blocked by DENV NS2B3 protease. The molecular target of dengue protease in IFN induction was mediator of IRF3 activation (MITA) but not the murine homologue MPYS. MITA, also known as stimulator of interferon genes (STING), is an ER-localized transmembrane protein essential for IFN induction. The cleavage site of MITA by dengue NS3B3 was mapped to LRR↓⁹⁶G and this cleavage resulted in impaired MITA activation. DENV replication increased when the endogenous MITA was silenced supporting the notion that MITA plays a role in IFN signaling during DENV infection. Furthermore, the author found thatMITA and dengue NS2B3 physically interact with each other, and this interaction could be further enhanced by stimulation with poly (dA:dT). In sum, this study identified that DENV subverts the host innate immunity by cleaving MITA through a dengue protease-dependent mechanism.

Reference

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