African swine fever virus enhances viral replication by increasing intracellular reduced glutathione levels, which suppresses stress granule formation.

IF 3.7 1区 农林科学 Q1 VETERINARY SCIENCES
Han Gao, Taoming Gu, Xiaopeng Gao, Zebu Song, Jing Liu, Yi Song, Guihong Zhang, Yankuo Sun
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Abstract

African swine fever virus (ASFV) is a DNA virus that has significantly impacted the global swine industry. Currently, there are no effective therapies or vaccines against ASFV. Stress granules (SGs), known for their antiviral properties, are not induced during ASFV infection, even though reactive oxygen species (ROS) are generated. The mechanism by which ASFV regulates SGs formation remains unclear. This study demonstrates that ASFV antagonises SGs formation and increases intracellular levels of reduced glutathione (GSH) levels. The use of the GSH inhibitor BSO and the activator NAC confirmed that the ASFV-induced increase in GSH helps to suppress SGs formation and influences viral replication. Additionally, this study revealed that ASFV enhances GSH by upregulating the antioxidant transcription factor NRF2, as well as factors involved in GSH synthesis and regeneration, such as GCLC, and those related to the ferroptosis pathway, such as SLC7A11. Furthermore, the study uncovered that ASFV manipulates intracellular GSH levels by activating the mitochondrial protein AIFM1. This regulatory mechanism helps the virus inhibit the formation of intracellular SGs, thereby creating an optimal environment for viral replication. These findings provide new insights into the molecular strategies employed by ASFV.

非洲猪瘟病毒通过增加细胞内还原型谷胱甘肽水平来增强病毒复制,从而抑制应激颗粒的形成。
非洲猪瘟病毒(ASFV)是一种DNA病毒,严重影响了全球养猪业。目前,还没有针对非洲猪瘟的有效疗法或疫苗。应激颗粒(SGs)以其抗病毒特性而闻名,在ASFV感染期间不会被诱导,即使产生活性氧(ROS)。ASFV调控SGs形成的机制尚不清楚。该研究表明,ASFV可拮抗SGs形成并增加细胞内还原型谷胱甘肽(GSH)水平。GSH抑制剂BSO和激活剂NAC的使用证实,asfv诱导的GSH增加有助于抑制SGs的形成并影响病毒复制。此外,本研究还发现ASFV通过上调抗氧化转录因子NRF2以及参与GSH合成和再生的因子(如GCLC)和与铁死亡途径相关的因子(如SLC7A11)来增强GSH。此外,该研究发现ASFV通过激活线粒体蛋白AIFM1来操纵细胞内GSH水平。这种调节机制有助于病毒抑制细胞内SGs的形成,从而为病毒复制创造最佳环境。这些发现为ASFV采用的分子策略提供了新的见解。
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来源期刊
Veterinary Research
Veterinary Research 农林科学-兽医学
CiteScore
7.00
自引率
4.50%
发文量
92
审稿时长
3 months
期刊介绍: Veterinary Research is an open access journal that publishes high quality and novel research and review articles focusing on all aspects of infectious diseases and host-pathogen interaction in animals.
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