title: SUMOylation of nonstructural 5A protein regulates hepatitis C virus replication.
abstract: Viruses exploit cellular SUMOylation machinery to favour their own propagation. We show that NS5A is a target protein of small ubiquitin-like modifier (SUMO) and is SUMOylated at lysine residue 348. We demonstrated that SUMOylation increased protein stability of NS5A by inhibiting ubiquitylation, and SUMOylation was also required for protein interaction with NS5B. These data imply that SUMO modification may contribute to HCV replication. Indeed, silencing of UBC9 impaired HCV replication in Jc1-infected cells, and HCV replication level was also significantly reduced in SUMO-defective subgenomic replicon cells. Taken together, these data indicate that HCV replication is regulated by SUMO modification of NS5A protein. We provide evidence for the first time that HCV exploits host cellular SUMO modification system to favour its own replication.
authors.affiliation: National Research Laboratory of Hepatitis C Virus, Ilsong Institute of Life Science, Hallym University, Anyang, Korea.
authors.forename: H S
authors.initials: HS
authors.lastname: Lee
authors.forename: Y S
authors.initials: YS
authors.lastname: Lim
authors.forename: E M
authors.initials: EM
authors.lastname: Park
authors.forename: S H
authors.initials: SH
authors.lastname: Baek
authors.forename: S B
authors.initials: SB
authors.lastname: Hwang
mesh_terms: D020868:Gene Silencing; D016174:Hepacivirus / Q000502:physiology*; D054884:Host-Pathogen Interactions; D025941:Protein Interaction Mapping; D055550:Protein Stability; D025841:Small Ubiquitin-Related Modifier Proteins / Q000378:metabolism*; D058207:Sumoylation; D044763:Ubiquitin-Conjugating Enzymes / Q000235:genetics / Q000378:metabolism*; D017361:Viral Nonstructural Proteins / Q000378:metabolism*; D014779:Virus Replication; D000098843:Ubiquitin-Conjugating Enzyme UBC9; D012324:RNA-Dependent RNA Polymerase
chemical_list: D025841:Small Ubiquitin-Related Modifier Proteins; D044763:Ubiquitin-Conjugating Enzymes; D017361:Viral Nonstructural Proteins; D000098843:Ubiquitin-Conjugating Enzyme UBC9; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase
keywords: HCV replication; NS5A; SUMOylation; hepatitis C virus; protein stability