Nuclear receptor 4 group A member 1 determines hepatitis C virus entry efficiency through the regulation of cellular receptor and apolipoprotein E expression.

 　　The 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. The expression of NR4A1 in Huh7.5.1 cells was significantly upregulated by 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 viral 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 SR-BI, Occludin, Claudin-1, and EGFR, but not CD81. The reduced specific infectivity of HCV in the knockdown cells was due to the decreased apolipoprotein E (ApoE) expression. These results explained 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.

http://vir.sgmjournals.org/content/early/2014/04/17/vir.0.065003-0.short?rss=1