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J Hepatol. 2007 Mar;46(3):411-9. Epub 2006 Nov 13.

The low-density lipoprotein receptor plays a role in the infection of primary human hepatocytes by hepatitis C virus.

Author information

1
Inserm, U632, Hepatic Physiopathology, 1919 route de Mende, 34293 Montpellier Cedex 5, France.

Abstract

BACKGROUND/AIMS:

The direct implication of low-density lipoprotein receptor (LDLR) in hepatitis C virus (HCV) infection of human hepatocyte has not been demonstrated. Normal primary human hepatocytes infected by serum HCV were used to document this point.

METHODS:

Expression and activity of LDLR were assessed by RT-PCR and LDL entry, in the absence or presence of squalestatin or 25-hydroxycholesterol that up- or down-regulates LDLR expression, respectively. Infection was performed in the absence or presence of LDL, HDL, recombinant soluble LDLR peptides encompassing full-length (r-shLDLR4-292) or truncated (r-shLDLR4-166) LDL-binding domain, monoclonal antibodies against r-shLDLR4-292, squalestatin or 25-hydroxycholesterol. Intracellular amounts of replicative and genomic HCV RNA strands used as end point of infection were assessed by RT-PCR.

RESULTS:

r-shLDLR4-292, antibodies against r-shLDLR4-292 and LDL inhibited viral RNA accumulation, irrespective of genotype, viral load or liver donor. Inhibition was greatest when r-shLDLR4-292 was present at the time of inoculation and gradually decreased as the delay between inoculation and r-shLDLR4-292 treatment increased. In hepatocytes pre-treated with squalestatin or 25-hydroxycholesterol before infection, viral RNA accumulation increased or decreased in parallel with LDLR mRNA expression and LDL entry.

CONCLUSIONS:

LDLR is involved at an early stage in infection of normal human hepatocytes by serum-derived HCV virions.

PMID:
17156886
DOI:
10.1016/j.jhep.2006.09.024
[Indexed for MEDLINE]
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