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

Viruses. 2019 Jun 11;11(6):544. doi: 10.3390/v11060544.

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.

Keywords: 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR); adenosine 5′-monophosphate (AMP)-activated protein kinase (AMPK); interaction; porcine circovirus type 2 (PCV2); protein phosphatase 2 (PP2A).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AMP-Activated Protein Kinase Kinases
  • Animals
  • Cell Line
  • Circovirus / growth & development*
  • Circovirus / immunology*
  • Host-Pathogen Interactions*
  • Hydroxymethylglutaryl CoA Reductases / metabolism*
  • Protein Binding
  • Protein Kinases / metabolism
  • Protein Phosphatase 2 / metabolism
  • Swine
  • Viral Proteins / antagonists & inhibitors*
  • Viral Proteins / metabolism*

Substances

  • Viral Proteins
  • Hydroxymethylglutaryl CoA Reductases
  • Protein Kinases
  • AMP-Activated Protein Kinase Kinases
  • Protein Phosphatase 2