1. Academic Validation
  2. Pseudorabies Virus Inhibits Expression of Liver X Receptors to Assist Viral Infection

Pseudorabies Virus Inhibits Expression of Liver X Receptors to Assist Viral Infection

  • Viruses. 2022 Mar 3;14(3):514. doi: 10.3390/v14030514.
Yi Wang 1 2 3 Guo-Li Li 1 2 3 Yan-Li Qi 1 2 3 Li-Yun Li 1 2 3 Lu-Fang Wang 1 2 3 Cong-Rong Wang 1 2 3 Xin-Rui Niu 1 2 3 Tao-Xue Liu 1 2 3 Jiang Wang 1 2 3 Guo-Yu Yang 2 3 4 5 Lei Zeng 1 2 3 Bei-Bei Chu 1 2 3 4
Affiliations

Affiliations

  • 1 College of Veterinary Medicine, Henan Agricultural University, Zhengzhou 450046, China.
  • 2 Key Laboratory of Animal Biochemistry and Nutrition, Ministry of Agriculture and Rural Affairs of the People's Republic of China, Zhengzhou 450046, China.
  • 3 Key Laboratory of Animal Growth and Development, Zhengzhou 450046, China.
  • 4 International Joint Research Center of National Animal Immunology, Henan Agricultural University, Zhengzhou 450046, China.
  • 5 College of Animal Science & Technology, Henan University of Animal Husbandry and Economy, Zhengzhou 450047, China.
Abstract

Pseudorabies virus (PRV) is a contagious herpesvirus that causes Aujeszky's disease and economic losses worldwide. Liver X receptors (LXRs) belong to the Nuclear Receptor Superfamily and are critical for the control of lipid homeostasis. However, the role of LXR in PRV Infection has not been fully established. In this study, we found that PRV Infection downregulated the mRNA and protein levels of LXRα and LXRβ in vitro and in vivo. Furthermore, we discovered that LXR activation suppressed PRV proliferation, while LXR inhibition promoted PRV proliferation. We demonstrated that LXR activation-mediated reduction of cellular Cholesterol was critical for the dynamics of PRV entry-dependent clathrin-coated pits. Replenishment of Cholesterol restored the dynamics of clathrin-coated pits and PRV entry under LXR activation conditions. Interestingly, T0901317, an LXR Agonist, prevented PRV Infection in mice. Our results support a model that PRV modulates LXR-regulated Cholesterol metabolism to facilitate viral proliferation.

Keywords

Liver X receptors; clathrin-coated pits; pseudorabies virus; viral entry.

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