ADP-ribosylation Factor-related Protein 1 Interacts with NS5A and Regulates Hepatitis C Virus Propagation

Sci Rep. 2016 Aug 23:6:31211. doi: 10.1038/srep31211.

Abstract

The life cycle of hepatitis C virus (HCV) is tightly coupled to the lipid metabolism of host cells. In order to identify host factors involved in HCV propagation, we have previously screened a small interfering RNA (siRNA) library targeting host genes that control lipid metabolism and lipid droplet (LD) formation using cell culture-grown HCV (HCVcc)-infected cells. In this study, we selected and characterized the gene encoding ADP-ribosylation factor-related protein 1 (ARFRP1). ARFRP1 is essential for LD growth and is involved in the regulation of lipolysis. siRNA-mediated knockdown of ARFRP1 significantly inhibited HCV replication in both subgenomic replicon cells and HCVcc-infected cells. ARFRP1 interacted with NS5A and NS5A partially colocalized with LD. Silencing of ARFRP1 abrogated HCV-induced LD growth and viral protein expressions. Moreover, ARFRP1 recruited synaptosomal-associated protein 23 (SNAP23) to sites in close proximity to LDs in HCV-infected cells. Silencing of ARFRP1 ablated relocalization of SNAP23 to LD. These data indicate that HCV regulates ARFRP1 for LD growth to facilitate viral propagation and thus ARFRP1 may be a potential target for antiviral therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADP-Ribosylation Factors / genetics
  • ADP-Ribosylation Factors / metabolism*
  • Binding Sites
  • Cell Line
  • Gene Knockdown Techniques
  • HEK293 Cells
  • Hepacivirus / physiology*
  • Host-Pathogen Interactions
  • Humans
  • Lipid Droplets / metabolism*
  • Lipid Metabolism
  • Lipolysis
  • Protein Binding
  • Qb-SNARE Proteins / metabolism*
  • Qc-SNARE Proteins / metabolism*
  • Viral Nonstructural Proteins / chemistry
  • Viral Nonstructural Proteins / metabolism*
  • Virus Replication*

Substances

  • Qb-SNARE Proteins
  • Qc-SNARE Proteins
  • SNAP23 protein, human
  • Viral Nonstructural Proteins
  • NS-5 protein, hepatitis C virus
  • ADP-Ribosylation Factors
  • ARFRP1 protein, human