Linked Life Data

17374756

Source:http://linkedlifedata.com/resource/pubmed/id/17374756

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
Pt 4
pubmed:dateCreated
2007-3-21
pubmed:abstractText
Folding and assembly into complexes of some viral glycoproteins are exquisitely sensitive to endoplasmic reticulum (ER) alpha-glucosidase inhibition, which prevents the trimming of glucose from N-linked glycans. Derivatives of deoxynojirimycin (DNJ) iminosugars, which are potent alpha-glucosidase inhibitors, were shown to have antiviral activity against bovine viral diarrhea virus, a pestivirus related to hepatitis C virus (HCV). The aim of this study was to determine whether these inhibitors would affect HCV infectivity and to provide novel insights on their mechanism of action. The overall antiviral activity of glucosidase inhibitors was shown by using the two most relevant models currently available: the cell-culture model enabling complete replication of the HCV JFH1 strain in Huh7.5 cells, and infectious HCV pseudotyped particles (HCVpp) produced in HEK-293T cells that display functional E1-E2 glycoprotein complexes. By using the latter model, it is shown that the inhibition of alpha-glucosidases by iminosugars results in the misfolding and misassembly of HCV glycoprotein pre-budding complexes. This inhibition of the assembly of E1-E2 in the ER of transfected HEK-293T cells leads to a reduction in the incorporation of E1-E2 complexes into HCVpp. More importantly, it is demonstrated that the infectivity of HCVpp that are released under treatment is reduced and that this reduction in infectivity is due to the incorporation of misfolded envelope glycoproteins in secreted particles. These properties suggest the potential usefulness of DNJ derivatives in combating HCV infection.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0022-1317
pubmed:author
pubmed:issnType
Print
pubmed:volume
88
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1133-43
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
Reduction of the infectivity of hepatitis C virus pseudoparticles by incorporation of misfolded glycoproteins induced by glucosidase inhibitors.
pubmed:affiliation
INSERM, U871, Université Lyon 1, et IFR62 Laennec, Lyon, France.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't