title: Hepatitis C Virus Nonstructural 5A Protein Interacts with Abelson Interactor 1 and Modulates Epidermal Growth Factor-mediated MEK/ERK Signaling Pathway.
abstract: The propagation of hepatitis C virus (HCV) is highly dependent on host cellular factors. To identify the cellular factors involved in HCV propagation, we have previously performed protein microarray assays using the HCV nonstructural 5A (NS5A) protein as a probe. Of ∼9,000 host proteins immobilized in a microarray, ∼90 cellular proteins were identified as HCV NS5A interacting partners. Of these candidates, we selected Abelson interactor 1 (Abi1) for further characterization. Binding of HCV NS5A to Abi1 was verified by both in vitro pulldown and coimmunoprecipitation assays. HCV NS5A interacted with Abi1 through regions I + II of Abi1 and domain I of NS5A. We further demonstrated that Abi1 colocalized with the HCV NS5A protein in the cytoplasm. We showed that NS5A inhibited epidermal growth factor-mediated ERK and Egr1 activations and this inhibitory activity of NS5A was nullified in Abi1-knockdown cells. Moreover, silencing of Abi1 expression impaired HCV replication, whereas overexpression of Abi1 promoted HCV propagation. Collectively, these data indicate that HCV exploits host Abi1 protein via NS5A to modulate MEK/ERK signaling pathway for its own propagation.
authors.affiliation: From the National Research Laboratory of Hepatitis C Virus and Ilsong Institute of Life Science, Hallym University, Anyang 14066, Korea.
authors.forename: Van T T
authors.initials: VT
authors.lastname: Huynh
authors.affiliation: From the National Research Laboratory of Hepatitis C Virus and Ilsong Institute of Life Science, Hallym University, Anyang 14066, Korea.
authors.forename: Yun-Sook
authors.initials: YS
authors.lastname: Lim
authors.affiliation: From the National Research Laboratory of Hepatitis C Virus and Ilsong Institute of Life Science, Hallym University, Anyang 14066, Korea.
authors.forename: Si C
authors.initials: SC
authors.lastname: Tran
authors.affiliation: From the National Research Laboratory of Hepatitis C Virus and Ilsong Institute of Life Science, Hallym University, Anyang 14066, Korea.
authors.forename: Tu M
authors.initials: TM
authors.lastname: Pham
authors.affiliation: From the National Research Laboratory of Hepatitis C Virus and Ilsong Institute of Life Science, Hallym University, Anyang 14066, Korea.
authors.forename: Lam N
authors.initials: LN
authors.lastname: Nguyen
authors.affiliation: From the National Research Laboratory of Hepatitis C Virus and Ilsong Institute of Life Science, Hallym University, Anyang 14066, Korea sbhwang@hallym.ac.kr.
authors.forename: Soon B
authors.initials: SB
authors.lastname: Hwang
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D051766:Early Growth Response Protein 1 / Q000235:genetics / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000235:genetics / Q000378:metabolism*; D020868:Gene Silencing; D016174:Hepacivirus / Q000502:physiology*; D006801:Humans; D020935:MAP Kinase Signaling System; D011485:Protein Binding; D017361:Viral Nonstructural Proteins / Q000235:genetics / Q000378:metabolism*; D014779:Virus Replication / Q000502:physiology*; D012324:RNA-Dependent RNA Polymerase
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D003598:Cytoskeletal Proteins; D051766:Early Growth Response Protein 1; D004815:Epidermal Growth Factor; D017361:Viral Nonstructural Proteins; C513733:ABI1 protein, human; C497325:EGR1 protein, human; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase
keywords: early growth response protein 1 (EGR1); epidermal growth factor (EGF); extracellular-signal-regulated kinase (ERK); growth factor receptor-bound protein 2 (GRB2); hepatitis C virus (HCV); signal transduction