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

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

  • Vet Res. 2024 Dec 20;55(1):172. doi: 10.1186/s13567-024-01433-4.
Han Gao 1 2 3 4 5 6,  Taoming Gu 1 2 3 4,  Xiaopeng Gao 1 2 3 4,  Zebu Song 1 2 3 4,  Jing Liu 1 2 3 4,  Yi Song 1 2 3 4,  Guihong Zhang 7 8 9 10,  Yankuo Sun 11 12 13 14
Affiliations

Affiliations

  • 1 African Swine Fever Regional Laboratory of China (Guangzhou), South China Agricultural University, Guangzhou, 510642, China.
  • 2 College of Veterinary Medicine, South China Agricultural University, Guangzhou, 510642, China.
  • 3 Guangdong Provincial Key Laboratory of Zoonosis Prevention and Control, College of Veterinary Medicine, South China Agricultural University, Guangzhou, 510642, China.
  • 4 Maoming Branch, Guangdong Laboratory for Lingnan Modern Agriculture, Maoming, 525000, China.
  • 5 School of Animal Science and Technology, Foshan University, Foshan, 528225, China.
  • 6 Guangdong Provincial Key Laboratory of Animal Molecular Design and Precise Breeding, College of Animal Science and Technology, Foshan University, Foshan, 528225, China.
  • 7 African Swine Fever Regional Laboratory of China (Guangzhou), South China Agricultural University, Guangzhou, 510642, China. guihongzh@scau.edu.cn.
  • 8 College of Veterinary Medicine, South China Agricultural University, Guangzhou, 510642, China. guihongzh@scau.edu.cn.
  • 9 Guangdong Provincial Key Laboratory of Zoonosis Prevention and Control, College of Veterinary Medicine, South China Agricultural University, Guangzhou, 510642, China. guihongzh@scau.edu.cn.
  • 10 Maoming Branch, Guangdong Laboratory for Lingnan Modern Agriculture, Maoming, 525000, China. guihongzh@scau.edu.cn.
  • 11 African Swine Fever Regional Laboratory of China (Guangzhou), South China Agricultural University, Guangzhou, 510642, China. yankuosun@scau.edu.cn.
  • 12 College of Veterinary Medicine, South China Agricultural University, Guangzhou, 510642, China. yankuosun@scau.edu.cn.
  • 13 Guangdong Provincial Key Laboratory of Zoonosis Prevention and Control, College of Veterinary Medicine, South China Agricultural University, Guangzhou, 510642, China. yankuosun@scau.edu.cn.
  • 14 Maoming Branch, Guangdong Laboratory for Lingnan Modern Agriculture, Maoming, 525000, China. yankuosun@scau.edu.cn.
PMID: 39707514 DOI: 10.1186/s13567-024-01433-4
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.

Keywords

African swine fever virus (ASFV); reduced glutathione (GSH); stress granules (SGs).

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