2. Academic Validation
  3. HDAC4 suppresses porcine epidemic diarrhea virus infection through negatively regulating MEF2A-GLUT1/3 axis- mediated glucose uptake

HDAC4 suppresses porcine epidemic diarrhea virus infection through negatively regulating MEF2A-GLUT1/3 axis- mediated glucose uptake

  • Vet Microbiol. 2025 Jun:305:110520. doi: 10.1016/j.vetmic.2025.110520.
Xiaomin Wang 1,  Lei Wang 2,  Duan Li 1,  Yilong Liu 1,  Qi Shang 3,  Yanling Liu 1,  Leyi Zhang 4,  Zheng Xu 5,  Cuiqin Huang 6,  Changxu Song 7
Affiliations

Affiliations

  • 1 College of Animal Science, National Engineering Center for Swine Breeding Industry, State Key Laboratory of Swine and Poultry Breeding Industry, South China Agricultural University, Guangzhou, Guangdong 510642, PR China.
  • 2 College of Life Sciences, Engineering Research Center for the Prevention and Control of Animal Original Zoonosis of Fujian Province University, Longyan University, Longyan, Fujian 364012, PR China.
  • 3 Anhui Divinity Biological Products Co., LTD, Bozhou, Anhui 236800, PR China.
  • 4 College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan 625014, PR China.
  • 5 College of Animal Science, National Engineering Center for Swine Breeding Industry, State Key Laboratory of Swine and Poultry Breeding Industry, South China Agricultural University, Guangzhou, Guangdong 510642, PR China. Electronic address: stonezen@scau.edu.cn.
  • 6 College of Life Sciences, Engineering Research Center for the Prevention and Control of Animal Original Zoonosis of Fujian Province University, Longyan University, Longyan, Fujian 364012, PR China. Electronic address: cuiqinh@126.com.
  • 7 College of Animal Science, National Engineering Center for Swine Breeding Industry, State Key Laboratory of Swine and Poultry Breeding Industry, South China Agricultural University, Guangzhou, Guangdong 510642, PR China. Electronic address: cxsong2004@163.com.
PMID: 40250106 DOI: 10.1016/j.vetmic.2025.110520
Abstract

Porcine epidemic diarrhea virus (PEDV), a porcine enteropathogenic coronavirus, causes severe diarrhea and death in neonatal piglets. Histone deacetylase 4 (HDAC4), a member of class IIa deacetylases, controls a wide range of physiological processes, but, little is known about its role in PEDV Infection. Here, we report a novel strategy by which PEDV manipulates HDAC4. First, HDAC4 expression was examined, and showed a significant down-regulation in PEDV-infected Vero and IPEC-J2 cells. Subsequently, knockdown of HDAC4 by specific small interfering RNA (siRNA) led to an increase in viral Infection, whereas overexpression of HDAC4 remarkably suppressed PEDV Infection. Mechanistically, we showed that HDAC4 significantly reduced glucose uptake, as glucose is required for PEDV Infection. Through screening, we identified glucose transporters 1 and 3 (GLUT1 and GLUT3) as responsible for glucose uptake during PEDV Infection. We further confirmed that HDAC4 regulated GLUT1 and GLUT3 expression through its converging hub, myocyte enhancer factor 2 A (MEF2A). Taken together, these findings contribute to a better understanding of a novel function of HDAC4 in regulating glucose uptake via MEF2A-GLUT1/3 to limit PEDV Infection, and provide new strategies for the development of anti-PEDV drugs.

Keywords

GLUT; Glucose uptake; HDAC4; MEF2A; PEDV; Viral infection.

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