2. Academic Validation
  3. Deoxycholic acid inhibits ASFV replication by inhibiting MAPK signaling pathway

Deoxycholic acid inhibits ASFV replication by inhibiting MAPK signaling pathway

  • Int J Biol Macromol. 2024 Mar 15:130939. doi: 10.1016/j.ijbiomac.2024.130939.
Qi Gao 1,  Yifan Xu 2,  Yongzhi Feng 2,  Xiaoyu Zheng 3,  Ting Gong 4,  Qiyuan Kuang 2,  Qinxin Xiang 2,  Lang Gong 5,  Guihong Zhang 6
Affiliations

Affiliations

  • 1 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; Key Laboratory of Animal Vaccine Development, Ministry of Agriculture and Rural Affairs, Guangzhou 510000, China.
  • 2 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.
  • 3 Guangdong Provincial Key Laboratory of Zoonosis Prevention and Control, College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China; Maoming Branch, Guangdong Laboratory for Lingnan Modern Agriculture, Maoming 525000, China.
  • 4 Guangdong Provincial Key Laboratory of Zoonosis Prevention and Control, College of Veterinary Medicine, South China Agricultural University, 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.
  • 5 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; Key Laboratory of Animal Vaccine Development, Ministry of Agriculture and Rural Affairs, Guangzhou 510000, China. Electronic address: gonglang@scau.edu.cn.
  • 6 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; Key Laboratory of Animal Vaccine Development, Ministry of Agriculture and Rural Affairs, Guangzhou 510000, China. Electronic address: guihongzh@scau.edu.cn.
PMID: 38493816 DOI: 10.1016/j.ijbiomac.2024.130939
Abstract

African swine fever (ASF) is an acute, febrile, highly contagious Infection of pigs caused by the African swine fever virus (ASFV). The purpose of this study is to understand the molecular mechanism of ASFV Infection and evaluate the effect of DCA on MAPK pathway, so as to provide scientific basis for the development of new Antiviral drugs. The transcriptome analysis found that ASFV Infection up-regulated the IL-17 and MAPK signaling pathways to facilitate viral replication. Metabolome analysis showed that DCA levels were up-regulated after ASFV Infection, and that exogenous DCA could inhibit activation of the MAPK pathway by ASFV Infection and thus inhibit viral replication. Dual-luciferase reporter assays were used to screen the genes of ASFV and revealed that I73R could significantly up-regulate the transcription level of AP-1 transcription factor in the MAPK pathway. Confocal microscopy demonstrated that I73R could promote AP-1 entry into the nucleus, and that DCA could inhibit the I73R-mediated nuclear entry of AP-1, inhibiting MAPK pathway, and I73R interacts with AP-1. These results indicated that DCA can inhibit ASFV-mediated activation of the MAPK pathway, thus inhibiting ASFV replication. This study provides a theoretical basis for research on ASF pathogenesis and for Antiviral drug development.

Keywords

African swine fever virus; Deoxycholic acid; MAPK signaling pathway.

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