rig-i, mda5 and tlr3 synergistically play an important role in restriction of dengue virus infectionrig - i,mda5 tlr3协同发挥重要作用限制登革热病毒感染.pdfVIP

RIG-I, MDA5 and TLR3 Synergistically Play an Important Role in Restriction of Dengue Virus Infection 1 . 1. 2 3 3 A. M. A. Nasirudeen * , Hui Hui Wong , Peiling Thien , Shengli Xu , Kong-Peng Lam , Ding Xiang Liu1,2* 1 Institute of Molecular and Cell Biology, Singapore, Singapore, 2 School of Biological Sciences, Nanyang Technological University, Singapore, Singapore, 3 Immunology Group, Bioprocessing Technology Institute, Singapore, Singapore Abstract Dengue virus (DV) infection is one of the most common mosquito-borne viral diseases in the world. The innate immune system is important for the early detection of virus and for mounting a cascade of defense measures which include the production of type 1 interferon (IFN). Hence, a thorough understanding of the innate immune response during DV infection would be essential for our understanding of the DV pathogenesis. A recent application of the microarray to dengue virus type 1 (DV1) infected lung carcinoma cells revealed the increased expression of both extracellular and cytoplasmic pattern recognition receptors; retinoic acid inducible gene-I (RIG-I), melanoma differentiation associated gene-5 (MDA-5) and Toll- like receptor-3 (TLR3). These intracellular RNA sensors were previously reported to sense DV infection in different cells. In this study, we show that they are collectively involved in initiating an effective IFN production against DV. Cells silenced for these genes were highly susceptible to DV infection. RIG-I and MDA5 knockdown HUH-7 cells and TLR3 knockout macrophages were highly susceptible to DV infection. When cells were silenced for only RIG-I and MDA5 (but not TLR3), substantial production of IFN-b was observed upon virus infection a