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

Jiang Wang,Cong-Rong Wang,Guo-Yu Yang,Tao-Xue Liu,Lu-Fang Wang,Xin-Rui Niu,Guo-Li Li,Yi Wang,Li-Yun Li,Lei Zeng,Yan-Li Qi,Bei-Bei Chu

doi:10.3390/v14030514

Jiang Wang, Cong-Rong Wang + Show 10 more

Open Access

https://doi.org/10.3390/v14030514

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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.

Highlights

Pseudorabies (PR), called Aujeszky’s disease, is a highly infectious disease caused by the PR virus (PRV), which is a member of the subfamily Alphaherpesvirinae of the family Herpesviridae
To determine the role of Liver X receptors (LXRs) in PRV infection, we evaluated the expression of LXR
We examined whether cholesterol replenishment rescued PRV entry during LXR activation. Quantitative Real-Time PCR (qRT-PCR) indicated that PRV genome copy number in T0901317treated PK-15 cells was gradually increased with the concentration of cholesterol (Figure 5C)

Summary

Introduction

Pseudorabies (PR), called Aujeszky’s disease, is a highly infectious disease caused by the PR virus (PRV), which is a member of the subfamily Alphaherpesvirinae of the family Herpesviridae. The genome of PRV is approximately 143 kb encoding at least. PRV can infect a wide variety of mammals, including pigs, sheep, and cattle, causing severe clinical symptoms and death [2]. Scientists have been trying to develop diagnostic approaches and vaccines in recent years, PR remains an important infectious disease that is prevalent in many countries. Several recent reports have suggested that PRV can cause human endophthalmitis and encephalitis [3–5]. These findings indicate that PRV infection is a potential public health risk and not limited to the swine industry. New methods are urgently needed to prevent PRV infection

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