title: Nuclear receptor 4 group A member 1 determines hepatitis C virus entry efficiency through the regulation of cellular receptor and apolipoprotein E expression.
abstract: Orphan nuclear receptor subfamily 4 group A member 1 (NR4A1) is a transcription factor stimulated by many factors and plays pivotal roles in metabolism, proliferation and apoptosis. In this study, the expression of NR4A1 in Huh7.5.1 cells was significantly upregulated by hepatitis C virus (HCV) infection. The silencing of NR4A1 inhibited the entry of HCV and reduced the specific infectivity of secreted HCV particles but had only minor or no effect on the genome replication and translation, virion assembly and virus release steps of the virus life cycle. Further experiments demonstrated that the silencing of NR4A1 affected virus entry through pan-downregulation of the expression of HCV receptors scavenger receptor BI, occludin, claudin-1 and epidermal growth factor receptor but not CD81. The reduced specific infectivity of HCV in the knockdown cells was due to decreased apolipoprotein E (ApoE) expression. These results explain the delayed spread of HCV in NR4A1 knockdown Huh7.5.1 cells. Thus, NR4A1 plays a role in HCV replication through regulating the expression of HCV receptors and ApoE, and facilitates HCV entry and spread.
authors.affiliation: University of Chinese Academy of Sciences, Beijing, PR China.|State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, PR China.
authors.forename: Wandi
authors.initials: W
authors.lastname: Zhu
authors.affiliation: State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, PR China.
authors.forename: Rongjuan
authors.initials: R
authors.lastname: Pei
authors.affiliation: University of Chinese Academy of Sciences, Beijing, PR China.|State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, PR China.
authors.forename: Rui
authors.initials: R
authors.lastname: Jin
authors.affiliation: State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, PR China.
authors.forename: Xue
authors.initials: X
authors.lastname: Hu
authors.affiliation: State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, PR China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, PR China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, PR China.
authors.forename: Chunchen
authors.initials: C
authors.lastname: Wu
authors.affiliation: Institute of Virology, University hospital Essen, University of Duisburg-Essen, Essen, Germany.|State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, PR China.
authors.forename: Mengji
authors.initials: M
authors.lastname: Lu
authors.affiliation: State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, PR China.
authors.forename: Xinwen
authors.initials: X
authors.lastname: Chen
mesh_terms: D001057:Apolipoproteins E / Q000096:biosynthesis*; D045744:Cell Line, Tumor; D005786:Gene Expression Regulation; D020868:Gene Silencing; D016174:Hepacivirus / Q000502:physiology*; D022781:Hepatocytes / Q000821:virology*; D006801:Humans; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011991:Receptors, Virus / Q000096:biosynthesis*; D053586:Virus Internalization
chemical_list: D001057:Apolipoproteins E; C539821:NR4A1 protein, human; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D011991:Receptors, Virus