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犬干扰素基因刺激因子(STING)的鉴定与功能分析。

Identification and function analysis of canine stimulator of interferon gene (STING).

机构信息

MOE International Joint Collaborative Research Laboratory for Animal Health & Food Safety, Jiangsu Engineering Laboratory of Animal Immunology, Institute of Immunology, Nanjing Agricultural University, Nanjing, China.

MOE International Joint Collaborative Research Laboratory for Animal Health & Food Safety, Jiangsu Engineering Laboratory of Animal Immunology, Institute of Immunology, Nanjing Agricultural University, Nanjing, China.

出版信息

Microb Pathog. 2017 Dec;113:202-208. doi: 10.1016/j.micpath.2017.10.047. Epub 2017 Oct 24.

Abstract

Stimulator of interferon gene (STING) plays an important role in the cyclic GMP-AMP synthase (cGAS)-mediated activation of type I IFN responses. In this study, we identified and cloned canine STING gene. Full-length STING encodes a 375 amino acid product that shares the highest similarity with feline STING. Highest levels of mRNA of canine STING were detected in the spleen and lungs while the lowest levels in the heart and muscle. Analysis of its cellular localization showed that STING is localizes to the endoplasmic reticulum. STING overexpression induced the IFN response via the IRF3 and NF-κB pathways and up-regulated the expression of ISG15 and viperin. However, knockdown of STING did not inhibit the IFN-β response triggered by poly(dA:dT), poly(I:C), or SeV. Finally, overexpression of STING significantly inhibited the replication of canine influenza virus H3N2. Collectively, our findings indicate that STING is involved in the regulation of the IFN-β pathway in canine.

摘要

干扰素基因刺激蛋白(STING)在环鸟苷酸-腺苷酸合成酶(cGAS)介导的 I 型干扰素反应激活中发挥重要作用。在本研究中,我们鉴定并克隆了犬 STING 基因。全长的 STING 编码一个 375 个氨基酸的产物,与猫科动物的 STING 具有最高的相似性。犬科 STING 的 mRNA 水平在脾脏和肺部中检测到最高,而在心脏和肌肉中检测到最低。细胞定位分析表明 STING 位于内质网。STING 的过表达通过 IRF3 和 NF-κB 通路诱导 IFN 反应,并上调 ISG15 和 viperin 的表达。然而,STING 的敲低并不抑制 poly(dA:dT)、poly(I:C)或 SeV 触发的 IFN-β 反应。最后,STING 的过表达显著抑制了犬流感病毒 H3N2 的复制。总之,我们的研究结果表明,STING 参与了犬科动物 IFN-β 通路的调节。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4a33/7127566/7a28b0c9bd4b/gr1_lrg.jpg

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