Apolipoprotein E on hepatitis C virion facilitates infection through interaction with low-density lipoprotein receptor.
Virology
; 394(1): 99-108, 2009 Nov 10.
Article
em En
| MEDLINE
| ID: mdl-19751943
ABSTRACT
Hepatitis C virus (HCV) infection is a major cause of liver disease. HCV associates with host apolipoproteins and enters hepatocytes through complex processes involving some combination of CD81, claudin-1, occludin, and scavenger receptor BI. Here we show that infectious HCV resembles very low density lipoprotein (VLDL) and that entry involves co-receptor function of the low-density lipoprotein receptor (LDL-R). Blocking experiments demonstrate that beta-VLDL itself or anti-apolipoprotein E (apoE) antibody can block HCV entry. Knockdown of the LDL-R by treatment with 25-hydroxycholesterol or siRNA ablated ligand uptake and reduced HCV infection of cells, whereas infection was rescued upon cell ectopic LDL-R expression. Analyses of gradient-fractionated HCV demonstrate that apoE is associated with HCV virions exhibiting peak infectivity and dependence upon the LDL-R for cell entry. Our results define the LDL-R as a cooperative HCV co-receptor that supports viral entry and infectivity through interaction with apoE ligand present in an infectious HCV/lipoprotein complex comprising the virion. Disruption of HCV/LDL-R interactions by altering lipoprotein metabolism may therefore represent a focus for future therapy.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Apolipoproteínas E
/
Receptores Virais
/
Receptores de LDL
/
Hepacivirus
/
Ligação Viral
/
Internalização do Vírus
Limite:
Humans
Idioma:
En
Revista:
Virology
Ano de publicação:
2009
Tipo de documento:
Article
País de afiliação:
Estados Unidos