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首页> 外文期刊>PLOS Neglected Tropical Diseases >RIG-I, MDA5 and TLR3 Synergistically Play an Important Role in Restriction of Dengue Virus Infection
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RIG-I, MDA5 and TLR3 Synergistically Play an Important Role in Restriction of Dengue Virus Infection

机译：RIG-I，MDA5和TLR3协同作用在限制登革热病毒感染中起重要作用

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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-β was observed upon virus infection and vice versa. High susceptibility to virus infection led to ER-stress induced apoptosis in HUH-7 cells. Collectively, our studies demonstrate that the intracellular RNA virus sensors (RIG-I, MDA5 and TLR3) are activated upon DV infection and are essential for host defense against the virus.
机译：登革热病毒（DV）感染是世界上最常见的蚊媒病毒性疾病之一。先天免疫系统对于病毒的早期检测和采取一系列防御措施（包括产生1型干扰素（IFN））而言非常重要。因此，对DV感染期间先天免疫反应的透彻了解对于我们对DV发病机理的了解至关重要。微阵列在登革热病毒1型（DV1）感染的肺癌细胞中的最新应用表明，细胞外和细胞质模式识别受体的表达均增加。维甲酸诱导基因-I（RIG-I），黑色素瘤分化相关基因5（MDA-5）和Toll样受体3（TLR3）。这些细胞内RNA传感器以前被报道可以感应不同细胞中的DV感染。在这项研究中，我们表明他们共同参与了针对DV的有效IFN产生。这些基因沉默的细胞高度易受DV感染。 RIG-1和MDA5敲除的HUH-7细胞和TLR3敲除的巨噬细胞对DV感染高度敏感。当仅针对RIG-1和MDA5（而非TLR3）沉默细胞时，在病毒感染后观察到大量的IFN-β产生，反之亦然。病毒感染的高敏感性导致HUH-7细胞内质网应激诱导的细胞凋亡。总的来说，我们的研究表明细胞内RNA病毒传感器（RIG-1，MDA5和TLR3）在DV感染后被激活，并且是宿主抵抗病毒的必不可少的物质。

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