title: ADP-ribosylation Factor-related Protein 1 Interacts with NS5A and Regulates Hepatitis C Virus Propagation.
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.
authors.affiliation: National Research Laboratory of Hepatitis C Virus and Ilsong Institute of Life Science, Hallym University, Anyang, South Korea.
authors.forename: Yun-Sook
authors.initials: YS
authors.lastname: Lim
authors.affiliation: National Research Laboratory of Hepatitis C Virus and Ilsong Institute of Life Science, Hallym University, Anyang, South Korea.
authors.forename: Huong T T
authors.initials: HT
authors.lastname: Ngo
authors.affiliation: National Research Laboratory of Hepatitis C Virus and Ilsong Institute of Life Science, Hallym University, Anyang, South Korea.
authors.forename: Jihye
authors.initials: J
authors.lastname: Lee
authors.affiliation: National Research Laboratory of Hepatitis C Virus and Ilsong Institute of Life Science, Hallym University, Anyang, South Korea.
authors.forename: Kidong
authors.initials: K
authors.lastname: Son
authors.affiliation: National Research Laboratory of Hepatitis C Virus and Ilsong Institute of Life Science, Hallym University, Anyang, South Korea.|Korea National Institute of Health, Cheongwon-gun, South Korea.
authors.forename: Eun-Mee
authors.initials: EM
authors.lastname: Park
authors.affiliation: National Research Laboratory of Hepatitis C Virus and Ilsong Institute of Life Science, Hallym University, Anyang, South Korea.
authors.forename: Soon B
authors.initials: SB
authors.lastname: Hwang
mesh_terms: D020727:ADP-Ribosylation Factors / Q000235:genetics / Q000378:metabolism*; D001665:Binding Sites; D002460:Cell Line; D055785:Gene Knockdown Techniques; D057809:HEK293 Cells; D016174:Hepacivirus / Q000502:physiology*; D054884:Host-Pathogen Interactions; D006801:Humans; D066292:Lipid Droplets / Q000378:metabolism*; D050356:Lipid Metabolism; D008066:Lipolysis; D011485:Protein Binding; D050766:Qb-SNARE Proteins / Q000378:metabolism*; D050767:Qc-SNARE Proteins / Q000378:metabolism*; D017361:Viral Nonstructural Proteins / Q000737:chemistry / Q000378:metabolism*; D014779:Virus Replication; D012324:RNA-Dependent RNA Polymerase
chemical_list: D020727:ADP-Ribosylation Factors; D050766:Qb-SNARE Proteins; D050767:Qc-SNARE Proteins; D017361:Viral Nonstructural Proteins; C100493:SNAP23 protein, human; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase; C541296:ARFRP1 protein, human