Linked Life Data

19751943

Source:http://linkedlifedata.com/resource/pubmed/id/19751943

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2009-10-26
pubmed:abstractText
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.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1096-0341
pubmed:author
pubmed:issnType
Electronic
pubmed:day
10
pubmed:volume
394
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
99-108
pubmed:dateRevised
2011-2-10
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Apolipoprotein E on hepatitis C virion facilitates infection through interaction with low-density lipoprotein receptor.
pubmed:affiliation
Department of Immunology, University of Washington School of Medicine, Seattle, WA, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural