Inhibition of BET Family Proteins Suppresses African Swine Fever Virus Infection

Yaru Zhao, Qingli Niu, Saixia Yang, Jifei Yang, Zhonghui Zhang, Shuxian Geng, Jie Fan, Zhijie Liu, Guiquan Guan, Zhiqing Liu, Jia Zhou, Haitao Hu, Jianxun Luo, Hong Yin

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

African swine fever (ASF), an acute, severe, highly contagious disease caused by African swine fever virus (ASFV) infection in domestic pigs and boars, has a mortality rate of up to 100%. Because effective vaccines and treatments for ASF are lacking, effective control of the spread of ASF remains a great challenge for the pig industry. Host epigenetic regulation is essential for the viral gene transcription. Bromodomain and extraterminal (BET) family proteins, including BRD2, BRD3, BRD4, and BRDT, are epigenetic “readers” critical for gene transcription regulation. Among these proteins, BRD4 recognizes acetylated histones via its two bromodomains (BD1 and BD2) and recruits transcription factors, thereby playing a pivotal role in transcriptional regulation and chromatin remodeling during viral infection. However, how BET/BRD4 regulates ASFV replication and gene transcription is unknown. Here, we randomly selected 12 representative BET family inhibitors and compared their effects on ASFV infection in pig primary alveolar macrophages (PAMs). These were found to inhibit viral infection by interfering viral replication. The four most effective inhibitors (ARV-825, ZL0580, I-BET-762, and PLX51107) were selected for further antiviral activity analysis. These BET/BRD4 inhibitors dose dependently decreased the ASFV titer, viral RNA transcription, and protein production in PAMs. Collectively, we report novel function of BET/BRD4 inhibitors in inducing suppression of ASFV infection, providing insights into the role of BET/BRD4 in the epigenetic regulation of ASFV and potential new strategies for ASF prevention and control.

Original languageEnglish (US)
JournalMicrobiology Spectrum
Volume10
Issue number4
DOIs
StatePublished - Aug 2022
Externally publishedYes

Keywords

  • African swine fever virus
  • BET
  • BRD4
  • antiviral effect
  • inhibitors

ASJC Scopus subject areas

  • Physiology
  • Ecology
  • General Immunology and Microbiology
  • Genetics
  • Microbiology (medical)
  • Cell Biology
  • Infectious Diseases

Fingerprint

Dive into the research topics of 'Inhibition of BET Family Proteins Suppresses African Swine Fever Virus Infection'. Together they form a unique fingerprint.

Cite this