Retinoic Acid-inducible Gene I-inducible miR-23b Inhibits Infections by Minor Group Rhinoviruses through Down-regulation of the Very Low Density Lipoprotein Receptor
Retinoic Acid-inducible Gene I-inducible miR-23b Inhibits Infections by Minor Group Rhinoviruses through Down-regulation of the Very Low Density Lipoprotein Receptor
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DOI：
10.1074/jbc.m111.229856
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发表时间：
2011-07-22
影响因子：
4.8
通讯作者：
Fujita, Takashi
中科院分区：
文献类型：
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作者：
Ouda, Ryota;Onomoto, Koji;Fujita, Takashi
在哺乳动物中，病毒感染通过先天免疫受体检测，包括toll样受体和维甲酸诱导基因I （RIG-I）样受体（RLR），它们激活I型干扰素（IFN）系统。IFN本质上激活编码抗病毒蛋白的基因，抑制病毒复制的各个步骤，并促进随后获得性免疫反应的激活。在这项研究中，我们研究了非编码RNA在病毒感染或RLR激活时的表达。使用微阵列，我们鉴定了几种被RLR信号特异性诱导表达的microrna （miRNA）。根据生物信息学（miRBase Target Data base）的研究，rlr诱导的mirna之一miR-23b实际上降低了极低密度脂蛋白受体（VLDLR）和ldlr相关蛋白5 （LRP5）的表达。转染miR-23b特异性抑制鼻病毒1B （RV1B）的感染，RV1B利用低密度脂蛋白受体（LDLR）家族进入病毒。相反，anti-miRNA-23b的引入提高了病毒产量。利用小干扰RNA （siRNA）的敲低实验表明，VLDLR而不是LRP5对RV1B的有效感染至关重要。此外，转染感染性病毒RNA的实验显示，miR-23b不影响病毒进入后的复制。我们的研究结果强烈表明，RIG-I信号通过mir -23b介导的RV1B受体VLDLR的下调导致RV1B感染的抑制。
In mammals, viral infections are detected by innate immune receptors, including Toll-like receptor and retinoic acid inducible gene I (RIG-I)-like receptor (RLR), which activate the type I interferon (IFN) system. IFN essentially activates genes encoding antiviral proteins that inhibit various steps of viral replication as well as facilitate the subsequent activation of acquired immune responses. In this study, we investigated the expression of non-coding RNA upon viral infection or RLR activation. Using a microarray, we identified several microRNAs (miRNA) specifically induced to express by RLR signaling. As suggested by Bioinformatics (miRBase Target Data base), one of the RLR-inducible miRNAs, miR-23b, actually knocked down the expression of very low density lipoprotein receptor (VLDLR) and LDLR-related protein 5 (LRP5). Transfection of miR-23b specifically inhibited infection of rhinovirus 1B (RV1B), which utilizes the low density lipoprotein receptor (LDLR) family for viral entry. Conversely, introduction of anti-miRNA-23b enhanced the viral yield. Knockdown experiments using small interfering RNA (siRNA) revealed that VLDLR, but not LRP5, is critical for an efficient infection by RV1B. Furthermore, experiments with the transfection of infectious viral RNA revealed that miR-23b did not affect post-entry viral replication. Our results strongly suggest that RIG-I signaling results in the inhibitions of infections of RV1B through the miR-23b-mediated down-regulation of its receptor VLDLR.