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

• Published in: Viruses Vol. 14; no. 3; p. 514
• Main Authors: Wang, Yi, Li, Guo-Li, Qi, Yan-Li, Li, Li-Yun, Wang, Lu-Fang, Wang, Cong-Rong, Niu, Xin-Rui, Liu, Tao-Xue, Wang, Jiang, Yang, Guo-Yu, Zeng, Lei, Chu, Bei-Bei
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 03.03.2022; MDPI
• Subjects: agonists; Animals; Antibodies; Cholesterol; cholesterol metabolism; Clathrin; clathrin-coated pits; Coated pits; Flow cytometry; Genomes; Hepatitis; Herpesvirus 1, Suid - genetics; Herpesvirus 1, Suid - metabolism; Homeostasis; Homogenization; Infections; Infectious diseases; Ligands; Lipid metabolism; Lipids; liver; Liver X receptors; Liver X Receptors - genetics; Liver X Receptors - metabolism; Metabolism; Mice; mRNA; Phosphatase; Plasmids; Proteins; Pseudorabies; pseudorabies virus; Reagents; Suid alphaherpesvirus 1; Transcription factors; Veterinary medicine; viral entry; Viral infections; Viruses; United States > US; China; viral entry; Liver X receptors; clathrin-coated pits; pseudorabies virus
• ISSN: 1999-4915; 1999-4915
• DOI: 10.3390/v14030514

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.