Porcine HMGCR Inhibits Porcine Circovirus Type 2 Infection by Directly Interacting with the Viral Proteins.

Xinwei Zhang,Hongsheng Ouyang,Xiaohua Liu,Shiqi Zhang,Yulu Geng,Guyu Niu,Daxin Pang,Ting Ouyang,Linzhu Ren,Yifang Zhang

doi:10.3390/v11060544

Xinwei Zhang, Hongsheng Ouyang + Show 8 more

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https://doi.org/10.3390/v11060544

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Journal: Viruses	Publication Date: Jun 11, 2019
Citations: 6	License type: CC BY 4.0

Affiliation: Jilin University, Yunnan Agricultural University

Abstract

Porcine circovirus type 2 (PCV2) is the etiological agent of porcine circovirus diseases and porcine circovirus-associated diseases (PCVDs/PCVADs). However, the pathogenesis of PCV2 is not fully understood. We previously found that 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) is negatively associated with PCV2 infection in vitro and in vivo. HMGCR inhibits the early stages of PCV2 infection, while PCV2 infection induces the phosphorylation of HMGCR to inactivate the protein. In this study, we investigated the possibility that adenosine 5′-monophosphate (AMP)-activated protein kinase (AMPK), and protein phosphatase 2 (PP2A) participate in HMGCR-mediated inhibition of PCV2 infection and the interaction of porcine HMGCR with PCV2 proteins. The results showed that AMPK activity fluctuated in cells during the early stage of PCV2 infection, while PP2A had little effect on PCV2 infection and HMGCR activity. Furthermore, PCV2 infection may enhance or maintain the level of phosphorylated HMGCR by directly interacting with the protein in PK-15 cells. These findings may provide a better understanding of PCV2 pathogenesis, and HMGCR may be a novel PCV2 antiviral target.

Highlights

Porcine circovirus type 2 (PCV2) is the etiological agent of porcine circovirus diseases and porcine circovirus-associated diseases (PCVDs/PCVADs), which are present in every major swine-producing country in the world [1,2,3]
10 hpi and decreased at the other times, which is consistent with the results shown in Figures 1 and further confirm that AMPK activity fluctuated during the early stage of PCV2 infection
To examine whether the negative effect of hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) on the replication of PCV2 is associated with the viral Cap protein, we investigated the interaction and colocalization of HMGCR with the Cap protein during PCV2 infection using an immunofluorescence assay

Summary

Introduction

Porcine circovirus type 2 (PCV2) is the etiological agent of porcine circovirus diseases and porcine circovirus-associated diseases (PCVDs/PCVADs), which are present in every major swine-producing country in the world [1,2,3]. The pathogenesis of PCV2 is not fully understood. Due to its small genomic size (1.7 kb) and highly limited coding capacity, the life cycle of PCV2 relies predominantly on host cell factors [1]. Finding and identifying host proteins related to PCV2 infection is a promising strategy for elucidating PCV2 pathogenesis and controlling the viral infection. The enzyme 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) is the rate-controlling enzyme of the mevalonate pathway, which produces cholesterol and other isoprenoids [5].

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