Theaflavin inhibits African swine fever virus replication by disrupting lipid metabolism through activation of the AMPK signaling pathway in virto

Yang Chen; Zhi Wei; Zebu Song; Hao Chang; Yanchen Guo; Yankuo Sun; Heng Wang; Zezhong Zheng; Guihong Zhang

Virus Research (Sep 2023)

Theaflavin inhibits African swine fever virus replication by disrupting lipid metabolism through activation of the AMPK signaling pathway in virto

Yang Chen,
Zhi Wei,
Zebu Song,
Hao Chang,
Yanchen Guo,
Yankuo Sun,
Heng Wang,
Zezhong Zheng,
Guihong Zhang

Affiliations

Yang Chen: Guangdong Provincial Key Laboratory of Zoonosis Prevention and Control, College of Veterinary Medicine, South China Agricultural University, Guangzhou, China; African Swine Fever Regional Laboratory of China (Guangzhou), Guangzhou, China
Zhi Wei: Guangdong Provincial Key Laboratory of Zoonosis Prevention and Control, College of Veterinary Medicine, South China Agricultural University, Guangzhou, China; African Swine Fever Regional Laboratory of China (Guangzhou), Guangzhou, China
Zebu Song: Guangdong Provincial Key Laboratory of Zoonosis Prevention and Control, College of Veterinary Medicine, South China Agricultural University, Guangzhou, China; African Swine Fever Regional Laboratory of China (Guangzhou), Guangzhou, China
Hao Chang: Guangdong Provincial Key Laboratory of Zoonosis Prevention and Control, College of Veterinary Medicine, South China Agricultural University, Guangzhou, China; African Swine Fever Regional Laboratory of China (Guangzhou), Guangzhou, China
Yanchen Guo: Guangdong Provincial Key Laboratory of Zoonosis Prevention and Control, College of Veterinary Medicine, South China Agricultural University, Guangzhou, China; African Swine Fever Regional Laboratory of China (Guangzhou), Guangzhou, China
Yankuo Sun: Guangdong Provincial Key Laboratory of Zoonosis Prevention and Control, College of Veterinary Medicine, South China Agricultural University, Guangzhou, China; African Swine Fever Regional Laboratory of China (Guangzhou), Guangzhou, China; Key Laboratory of Animal Vaccine Development, Ministry of Agriculture and Rural Affairs, China
Heng Wang: Guangdong Provincial Key Laboratory of Zoonosis Prevention and Control, College of Veterinary Medicine, South China Agricultural University, Guangzhou, China; African Swine Fever Regional Laboratory of China (Guangzhou), Guangzhou, China; Key Laboratory of Animal Vaccine Development, Ministry of Agriculture and Rural Affairs, China
Zezhong Zheng: Guangdong Provincial Key Laboratory of Zoonosis Prevention and Control, College of Veterinary Medicine, South China Agricultural University, Guangzhou, China; African Swine Fever Regional Laboratory of China (Guangzhou), Guangzhou, China; Key Laboratory of Animal Vaccine Development, Ministry of Agriculture and Rural Affairs, China; Corresponding authors at: Guangdong Provincial Key Laboratory of Zoonosis Prevention and Control, College of Veterinary Medicine, South China Agricultural University, Guangzhou, China.
Guihong Zhang: Guangdong Provincial Key Laboratory of Zoonosis Prevention and Control, College of Veterinary Medicine, South China Agricultural University, Guangzhou, China; African Swine Fever Regional Laboratory of China (Guangzhou), Guangzhou, China; Maoming Branch, Guangdong Laboratory for Lingnan Modern Agriculture, Guangdong, China; Key Laboratory of Animal Vaccine Development, Ministry of Agriculture and Rural Affairs, China; Corresponding authors at: Guangdong Provincial Key Laboratory of Zoonosis Prevention and Control, College of Veterinary Medicine, South China Agricultural University, Guangzhou, China.

Journal volume & issue: Vol. 334
p. 199159

Abstract

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African swine fever virus (ASFV) is the etiological agent of African swine fever (ASF), which is one of the most harmful swine diseases in the pig industry because of its nearly 100% mortality rate in domestic pigs and results in incalculable economic loss. Ever since ASF was initially reported, scientists have worked to develop anti-ASF vaccines; however, currently no clinically effective vaccine for ASF is available. Therefore, the development of novel measures to prevent ASFV infection and transmission is essential. In this study, we aimed to investigate the anti-ASF activity of theaflavin (TF), a natural compound mainly isolated from black tea. We found that TF potently inhibited ASFV replication at non-cytotoxic concentrations ex vivo in primary porcine alveolar macrophages (PAMs). Mechanistically, we found that TF inhibited ASFV replication by acting on cells rather than interacting directly with ASFV to inhibit viral replication. Further, we found that TF upregulated the AMPK (5′-AMP-activated protein kinase) signaling pathway in ASFV-infected and uninfected cells, and treatment with the AMPK agonist MK8722 upregulated the AMPK signaling pathway and inhibited ASFV proliferation in a dose-dependent manner. Notably, the effects of TF on AMPK activation and ASFV inhibition were partially reversed by the AMPK inhibitor dorsomorphin. In addition, we found that TF down-regulated the expression of genes related to lipid synthesis and decreased the intracellular accumulation of total cholesterol and total triglycerides in ASFV-infected cells, suggesting that TF may inhibit ASFV replication by disrupting lipid metabolism. In summary, our results demonstrated that TF is an ASFV infection inhibitor and revealed the mechanism by which ASFV replication is inhibited, providing a novel mechanism and potential lead compound for the development of anti-ASFV drugs.

Published in Virus Research

ISSN: 1872-7492 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Microbiology; Medicine: Internal medicine: Infectious and parasitic diseases
Website: https://www.sciencedirect.com/journal/virus-research

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