Epstein–Barr virus infection controls the concentration of the intracellular antioxidant glutathione by upregulation of the glutamate transporter EAAT3 in tumor cells

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.

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Role of Oxidative Stress in the Epstein–Barr Virus Lifecycle and Tumorigenicity

Zhao

Luo

2023

Future Virol.

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The Epstein–Barr virus (EBV) is an oncogenic virus with both latent and lytic states during its lifecycle. EBV employs a latency period as a strategy to avoid host immune surveillance and achieve lifelong persistent infection. However, the latent state may be interrupted and EBV may reactivate into a lytic replication cycle, exacerbating transmission and pathogenicity. The balance and transition between these two phases in the EBV lifecycle are complex, and reactive oxygen species play an important role. We reviewed the relationship between oxidative stress and lytic replication of EBV, and the role of oxidative stress in the development of EBV-related tumors. Further research is required to explore and develop tumor antioxidant therapy.

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Epstein–Barr virus infection controls the concentration of the intracellular antioxidant glutathione by upregulation of the glutamate transporter EAAT3 in tumor cells

Cited by 3 publications

References 59 publications

Epstein–Barr Virus: Human Interactome Reveals New Molecular Insights into Viral Pathogenesis for Potential Therapeutics and Antiviral Drug Discovery

Epstein–Barr Virus: Human Interactome Reveals New Molecular Insights into Viral Pathogenesis for Potential Therapeutics and Antiviral Drug Discovery

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

Role of Oxidative Stress in the Epstein–Barr Virus Lifecycle and Tumorigenicity

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