Negative regulation of SREBP-1/FAS signaling molecules activates the RIG-1/TBK1-mediated IFN-I pathway to inhibit BVDV replication.

IF 4.5 2区 医学 Q1 PHARMACOLOGY & PHARMACY
Shanshan Liu, An Luo, Taolin Que, Yuxin Liang, Yuxin Song, Tianyi Liu, Jing Li, Nan Li, Zechen Zhang, Yu Liu, Zecai Zhang, Yulong Zhou, Xue Wang, Zhanbo Zhu
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引用次数: 0

Abstract

For many viruses, controlling the process of infection is largely dependent on the enzymes of the fatty acid synthesis (FAS) pathway. An appealing therapeutic target in antiviral research is fatty acid synthetase (FASN), a crucial enzyme in the FAS pathway. Bovine viral diarrhea, caused by the Bovine viral diarrhea virus (BVDV), is a significant viral infectious disease posing a substantial threat to global animal husbandry. Our study revealed that BVDV infection not only upregulates the expression of FAS-related enzymes in BT cells and the blood, liver, and spleen of mice but also markedly enhances the accumulation of lipid droplets, free fatty acids, and triglycerides. The FAS pathway plays a pivotal role throughout the entire BVDV replication cycle. Additionally, administration of the FASN inhibitor C75 and Acetyl CoA carboxylase-1 (ACC-1) inhibitor TOFA significantly reduced the viral content in both serum and organs of BVDV-infected mice, exhibiting inhibitory effects across diverse viral strains. Intriguingly, We found that RIG-1/TBK1-mediated IFN-I signaling inhibits SREBP-1/FAS and reduces BVDV replication. Conversely, targeting a few essential enzymes of SREBP-1/FAS also activates IFN-I signaling. More importantly, FASN inhibitor led to heightened expression of ISGs in mouse spleens by activating the RIG-1/TBK-1 pathway. These findings highlight that FASN inhibitors inhibit BVDV replication through the activation of the RIG-1/TBK-1 pathway to induce ISGs, and offering a novel therapeutic approach for combating BVDV. Thus, it is crucial to negatively regulate SREBP-1/FAS signaling molecules in order to create novel antiviral drugs that are safe, effective, and broad-spectrum.

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来源期刊
Antiviral research
Antiviral research 医学-病毒学
CiteScore
17.10
自引率
3.90%
发文量
157
审稿时长
34 days
期刊介绍: Antiviral Research is a journal that focuses on various aspects of controlling viral infections in both humans and animals. It is a platform for publishing research reports, short communications, review articles, and commentaries. The journal covers a wide range of topics including antiviral drugs, antibodies, and host-response modifiers. These topics encompass their synthesis, in vitro and in vivo testing, as well as mechanisms of action. Additionally, the journal also publishes studies on the development of new or improved vaccines against viral infections in humans. It delves into assessing the safety of drugs and vaccines, tracking the evolution of drug or vaccine-resistant viruses, and developing effective countermeasures. Another area of interest includes the identification and validation of new drug targets. The journal further explores laboratory animal models of viral diseases, investigates the pathogenesis of viral diseases, and examines the mechanisms by which viruses avoid host immune responses.
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