title: Hepatitis C virus NS5A competes with PI4KB for binding to ACBD3 in a genotype-dependent manner.
abstract: Although genotype-dependency of PI4KB involved in HCV replication has been reported, the mechanism underlying that is unknown. In this study, we found that NS5A and PI4KB competed for association of acyl-coenzyme A binding domain containing protein 3 (ACBD3), which inhibited HCV replication. ACBD3 bind to GT1b NS5A with a higher affinity than to GT2a NS5A, which was consistent with higher co-localization between PI4KB and phosphatidylinositol 4-phosphate (PI4P) in GT1b HCV-infected cells than that in GT2a HCV-infected cells. These results suggested that NS5A could rob the preexisting ACBD3/PI4KB complex to form NS5A/ACBD3 complex and PI4KB could relocate to the viral RNA replication sites to facilitate HCV replication. Our findings not only revealed the anti-HCV function of ACBD3, but also shed mechanistic light on how ACBD3 was manipulated by NS5A from different GT of HCV.
authors.affiliation: MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100176, China.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Hong
authors.affiliation: MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100176, China.
authors.forename: Xiaojie
authors.initials: X
authors.lastname: Yang
authors.affiliation: MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100176, China.
authors.forename: Guangbo
authors.initials: G
authors.lastname: Yang
authors.affiliation: MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100176, China. Electronic address: armzhang@hotmail.com.
authors.forename: Leiliang
authors.initials: L
authors.lastname: Zhang
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D005838:Genotype; D016174:Hepacivirus / Q000201:enzymology / Q000502:physiology*; D054884:Host-Pathogen Interactions; D008565:Membrane Proteins / Q000378:metabolism*; D015778:Minor Histocompatibility Antigens; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism*; D011485:Protein Binding; D017361:Viral Nonstructural Proteins / Q000378:metabolism*; D012324:RNA-Dependent RNA Polymerase
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D008565:Membrane Proteins; D015778:Minor Histocompatibility Antigens; D017853:Phosphotransferases (Alcohol Group Acceptor); D017361:Viral Nonstructural Proteins; C449459:ACBD3 protein, human; C402182:phosphatidylinositol phosphate 4-kinase; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase
keywords: ACBD3; HCV; NS5A; PI4KB; PI4P