TY - JOUR
T1 - Inhibition of BET Family Proteins Suppresses African Swine Fever Virus Infection
AU - Zhao, Yaru
AU - Niu, Qingli
AU - Yang, Saixia
AU - Yang, Jifei
AU - Zhang, Zhonghui
AU - Geng, Shuxian
AU - Fan, Jie
AU - Liu, Zhijie
AU - Guan, Guiquan
AU - Liu, Zhiqing
AU - Zhou, Jia
AU - Hu, Haitao
AU - Luo, Jianxun
AU - Yin, Hong
N1 - Publisher Copyright:
© 2022 American Society for Microbiology. All rights reserved.
PY - 2022/8
Y1 - 2022/8
N2 - 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.
AB - 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.
KW - African swine fever virus
KW - BET
KW - BRD4
KW - antiviral effect
KW - inhibitors
UR - http://www.scopus.com/inward/record.url?scp=85137137118&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85137137118&partnerID=8YFLogxK
U2 - 10.1128/spectrum.02419-21
DO - 10.1128/spectrum.02419-21
M3 - Article
C2 - 35758684
AN - SCOPUS:85137137118
SN - 2165-0497
VL - 10
JO - Microbiology Spectrum
JF - Microbiology Spectrum
IS - 4
ER -