RIG-I and TLR3 are both required for maximum interferon induction by influenza virus in human lung alveolar epithelial cells.

RIG-I and TLR3 are both required for maximum interferon induction by influenza virus in human lung alveolar epithelial cells.
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DOI:
10.1016/j.virol.2015.03.048
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发表时间:
2015-08
期刊:
影响因子:
3.7
通讯作者:
Metcalf, Jordan P.
Metcalf, Jordan P.
中科院分区:
医学3区
文献类型:
--
作者:
Wu, Wenxin;Zhang, Wei;Duggan, Elizabeth S.;Booth, J. Leland;Zou, Ming-Hui;Metcalf, Jordan P.

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模式识别受体,如视黄酸诱导蛋白I (RIG-I)、toll样受体3和7 (TLR3和7)以及核苷酸结合寡聚结构域蛋白2 (NOD2),在甲型流感病毒(IAV)的识别中发挥重要作用,但它们在干扰素(IFN)诱导中的作用尚不清楚,特别是在人肺中。我们研究了IAV在A549细胞系和原代人肺泡上皮细胞(AEC)中诱导IFN的作用。采用qRT-PCR和ELISA检测IAV PR8感染细胞中TLR3/7、NOD2、RIG-I和IFN的表达水平。我们发现在这些细胞中,TLR7和NOD2不参与IAV诱导IFN的过程。单独的RIG-I和TLR3 siRNA都不能完全阻断IFN的诱导。然而,rig - 1和TLR3的双敲低完全抑制流感诱导IFN。因此,通过rig - 1和TLR3的信号传导对于IAV在人肺AEC中诱导IFN是重要的。
Pattern recognition receptors, such as retinoic acid-inducible protein I (RIG-I), Toll-like receptors 3 and 7 (TLR3 and 7), and nucleotide-binding oligomerization domain containing protein 2 (NOD2), play important roles in the recognition of influenza A virus (IAV), but their role in interferon (IFN) induction is still unclear, particularly in human lung. We investigated IFN induction by IAV in the A549 cell line as well as in primary human alveolar epithelial cells (AEC). TLR3/7, NOD2, RIG-I, and IFN expression levels were measured by qRT-PCR and ELISA in cells infected with IAV PR8. We found that TLR7 and NOD2 were not involved in IFN induction by IAV in these cells. Neither RIG-I nor TLR3 siRNA alone completely blocked IFN induction. However, double knockdown of RIG-I and TLR3 completely inhibited IFN induction by influenza. Thus, signaling through both RIG-I and TLR3 is important for IFN induction by IAV in human lung AEC.
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