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STING 激动剂 SR717 对 PRRSV 复制的抑制作用。

Inhibition Effect of STING Agonist SR717 on PRRSV Replication.

机构信息

National International Joint Research Center for Animal Immunology, School of Animal Medicine, Henan Agricultural University, Zhengzhou 450046, China.

Key Laboratory of Animal Pathogenesis and Biosafety, Ministry of Education, School of Animal Medicine, Henan Agricultural University, Zhengzhou 450046, China.

出版信息

Viruses. 2024 Aug 29;16(9):1373. doi: 10.3390/v16091373.

DOI:10.3390/v16091373
PMID:39339849
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11437437/
Abstract

The porcine reproductive and respiratory syndrome virus (PRRSV) belongs to the Arteriviridae family and is a single-stranded, positively stranded RNA virus. The currently available PRRSV vaccines are mainly inactivated and attenuated vaccines, yet none of the commercial vaccines can provide comprehensive, long-lasting, and effective protection against PRRSV. SR717 is a pyridazine-3-carboxamide compound, which is commonly used as a non-nucleoside STING agonist with antitumor and antiviral activities. Nevertheless, there is no evidence that SR717 has any antiviral effects against PRRSV. In this study, a dose-dependent inhibitory effect of SR717 was observed against numerous strains of PRRSV using qRT-PCR, IFA, and WB methods. Furthermore, SR717 was found to stimulate the production of anti-viral molecules and trigger the activation of the signaling cascade known as the stimulator of interferon genes (STING) pathway, which contributed to hindering the reproduction of viruses by a certain margin. Collectively, these results indicate that SR717 is capable of inhibiting PRRSV infection in vitro and may have potential as an antiviral drug against PRRSV.

摘要

猪繁殖与呼吸综合征病毒(PRRSV)属于动脉炎病毒科,是一种单链、正链 RNA 病毒。目前可用的 PRRSV 疫苗主要是灭活疫苗和减毒疫苗,但没有一种商业疫苗能对 PRRSV 提供全面、持久和有效的保护。SR717 是一种哒嗪-3-甲酰胺化合物,通常用作具有抗肿瘤和抗病毒活性的非核苷 STING 激动剂。然而,没有证据表明 SR717 对 PRRSV 有任何抗病毒作用。在这项研究中,使用 qRT-PCR、IFA 和 WB 方法观察到 SR717 对多种 PRRSV 株具有剂量依赖性抑制作用。此外,SR717 被发现能刺激抗病毒分子的产生,并触发干扰素基因刺激物(STING)途径的信号级联反应的激活,这有助于在一定程度上抑制病毒的繁殖。总之,这些结果表明,SR717 能够抑制 PRRSV 在体外的感染,可能有潜力成为抗 PRRSV 的抗病毒药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a80/11437437/4d99ce79c8b1/viruses-16-01373-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a80/11437437/bd452d36ab77/viruses-16-01373-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a80/11437437/c927e4d4d051/viruses-16-01373-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a80/11437437/29b4bbfafaf8/viruses-16-01373-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a80/11437437/a019b8b489f1/viruses-16-01373-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a80/11437437/af9a4db2d2fe/viruses-16-01373-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a80/11437437/4d99ce79c8b1/viruses-16-01373-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a80/11437437/bd452d36ab77/viruses-16-01373-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a80/11437437/c927e4d4d051/viruses-16-01373-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a80/11437437/29b4bbfafaf8/viruses-16-01373-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a80/11437437/a019b8b489f1/viruses-16-01373-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a80/11437437/af9a4db2d2fe/viruses-16-01373-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a80/11437437/4d99ce79c8b1/viruses-16-01373-g006.jpg

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本文引用的文献

1
Transfer of cGAMP from neuron to microglia activates microglial type I interferon responses after subarachnoid hemorrhage.cGAMP 从神经元转移到小胶质细胞后,会在蛛网膜下腔出血后激活小胶质细胞的 I 型干扰素反应。
Cell Commun Signal. 2024 Jan 2;22(1):3. doi: 10.1186/s12964-023-01362-3.
2
The natural compound Sanggenon C inhibits PRRSV infection by regulating the TRAF2/NF-κB signalling pathway.天然化合物桑根酮 C 通过调节 TRAF2/NF-κB 信号通路抑制 PRRSV 感染。
Vet Res. 2023 Nov 30;54(1):114. doi: 10.1186/s13567-023-01245-y.
3
Synergistic Effects of Azithromycin and STING Agonist Promote IFN-I Production by Enhancing the Activation of STING-TBK1 Signaling.
阿奇霉素与STING激动剂的协同作用通过增强STING-TBK1信号通路的激活促进I型干扰素的产生。
J Exp Pharmacol. 2023 Nov 1;15:407-421. doi: 10.2147/JEP.S433181. eCollection 2023.
4
CBASS to cGAS-STING: The Origins and Mechanisms of Nucleotide Second Messenger Immune Signaling.从CBASS到cGAS-STING:核苷酸第二信使免疫信号的起源与机制
Annu Rev Virol. 2023 Sep 29;10(1):423-453. doi: 10.1146/annurev-virology-111821-115636. Epub 2023 Jun 28.
5
Interplay between RNA viruses and cGAS/STING axis in innate immunity.RNA 病毒与先天免疫中 cGAS/STING 轴的相互作用。
Front Cell Infect Microbiol. 2023 Apr 3;13:1172739. doi: 10.3389/fcimb.2023.1172739. eCollection 2023.
6
The Papain-Like Protease of Porcine Reproductive and Respiratory Syndrome Virus Impedes STING Translocation from the Endoplasmic Reticulum to the Golgi Apparatus by Deubiquitinating STIM1.猪繁殖与呼吸综合征病毒的木瓜蛋白酶样蛋白酶通过去泛素化 STIM1 来阻碍 STING 从内质网向高尔基体的易位。
J Virol. 2023 Apr 27;97(4):e0018823. doi: 10.1128/jvi.00188-23. Epub 2023 Apr 11.
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Flavonoid derivative DMXAA attenuates cisplatin-induced acute kidney injury independent of STING signaling.类黄酮衍生物DMXAA可减轻顺铂诱导的急性肾损伤,且不依赖于STING信号通路。
Clin Sci (Lond). 2023 Mar 31;137(6):435-452. doi: 10.1042/CS20220728.
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Nile tilapia DNA sensor STING is involved in the IFN-β and AP-1 signaling pathways in the immune response dependent on DDX41.尼罗罗非鱼DNA传感器STING参与依赖DDX41的免疫反应中的IFN-β和AP-1信号通路。
Int J Biol Macromol. 2023 Jan 15;225:27-39. doi: 10.1016/j.ijbiomac.2022.11.319. Epub 2022 Dec 7.
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Inhibition of the cGAS-STING Pathway Attenuates Lung Ischemia/Reperfusion Injury via Regulating Endoplasmic Reticulum Stress in Alveolar Epithelial Type II Cells of Rats.抑制cGAS-STING通路通过调节大鼠肺泡II型上皮细胞内质网应激减轻肺缺血/再灌注损伤
J Inflamm Res. 2022 Sep 5;15:5103-5119. doi: 10.2147/JIR.S365970. eCollection 2022.
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Pharmacological targeting of cGAS/STING-YAP axis suppresses pathological angiogenesis and ameliorates organ fibrosis.靶向 cGAS/STING-YAP 轴的药理学抑制病理性血管生成并改善器官纤维化。
Eur J Pharmacol. 2022 Oct 15;932:175241. doi: 10.1016/j.ejphar.2022.175241. Epub 2022 Sep 2.