2. Academic Validation
  3. African swine fever virus maintains de novo global cellular protein synthesis and inhibits stress granules formation via dephosphorylating eIF2α

African swine fever virus maintains de novo global cellular protein synthesis and inhibits stress granules formation via dephosphorylating eIF2α

  • Vet Microbiol. 2024 Jan 17:290:109988. doi: 10.1016/j.vetmic.2024.109988.
Han Gao 1,  Xiaopeng Gao 2,  Xing Liu 1,  Yizhuo Luo 1,  Jianhao Zhong 1,  Jing Liu 1,  Luling Yan 1,  Heng Wang 1,  Lang Gong 2,  Guihong Zhang 1,  Zezhong Zheng 3,  Yankuo Sun 4
Affiliations

Affiliations

  • 1 College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China; Guangdong Provincial Key Laboratory of Zoonosis Prevention and Control, College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China; African Swine Fever Regional Laboratory of China (Guangzhou), Guangzhou 510642, China; Maoming Branch, Guangdong Laboratory for Lingnan Modern Agriculture, Maoming 525000, China; Key Laboratory of Animal Vaccine Development, Ministry of Agriculture and Rural Affairs, Guangzhou 510000, China.
  • 2 College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China; Guangdong Provincial Key Laboratory of Zoonosis Prevention and Control, College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China; African Swine Fever Regional Laboratory of China (Guangzhou), Guangzhou 510642, China; Maoming Branch, Guangdong Laboratory for Lingnan Modern Agriculture, Maoming 525000, China.
  • 3 College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China; Guangdong Provincial Key Laboratory of Zoonosis Prevention and Control, College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China; African Swine Fever Regional Laboratory of China (Guangzhou), Guangzhou 510642, China; Maoming Branch, Guangdong Laboratory for Lingnan Modern Agriculture, Maoming 525000, China; Key Laboratory of Animal Vaccine Development, Ministry of Agriculture and Rural Affairs, Guangzhou 510000, China. Electronic address: [email protected].
  • 4 College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China; Guangdong Provincial Key Laboratory of Zoonosis Prevention and Control, College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China; African Swine Fever Regional Laboratory of China (Guangzhou), Guangzhou 510642, China; Maoming Branch, Guangdong Laboratory for Lingnan Modern Agriculture, Maoming 525000, China; Key Laboratory of Animal Vaccine Development, Ministry of Agriculture and Rural Affairs, Guangzhou 510000, China. Electronic address: [email protected].
PMID: 38244395 DOI: 10.1016/j.vetmic.2024.109988
Abstract

African swine fever virus (ASFV) has caused enormous economic losses since its first reported detection, and there is still no effective vaccines or drug treatment. During Infection, viruses may employ various strategies, such as regulating the host endoplasmic reticulum stress/unfolded protein response or the formation of stress granules (SGs), to form an optimal environment for virus replication. However, how ASFV Infection regulates host endoplasmic reticulum stress, eIF2α-regulated protein synthesis, and the formation of SGs remains unclear. Here, we evaluated the activation of ER stress and its three downstream axes during ASFV Infection and identified a powerful dephosphorylation of eIF2α by ASFV ex vivo. This strong dephosphorylation property could maintain the efficiency of eIF2α-mediated de novo global protein synthesis, thus ensuring efficient viral protein synthesis at early stage. In addition, the powerful dephosphorylation of eIF2α by ASFV upon Infection could also inhibit the formation of SGs induced by sodium arsenite. In addition, a specific eIF2α dephosphorylation inhibitor, salubrinal, could partially counteract ASFV-mediated eIF2α dephosphorylation and inhibit viral replication. Our results provide new insights into the areas of ASFV`s escape from host immunity and hijacking of the host protein translation system.

Keywords

African swine fever virus (ASFV); EIF2α phosphorylation/dephosphorylation; Endoplasmic reticulum (ER) stress; Protein synthesis; Stress granules (SGs).

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