Past
research has suggested that the low-density lipoprotein (LDL) cholesterol receptor
plays a role in hepatitis C virus (HCV) infection,
but the process is not well understood.
As
reported in the March 2007 Journal of Hepatology, in a laboratory study
French researchers assessed expression and activity of the LDL receptor in the
absence or presence of squalestatin (which up-regulates LDL receptor expression)
or 25-hydroxycholesterol (which down-regulates LDL receptor expression).
Human
hepatocytes were exposed to HCV in the absence or presence of LDL, high-density
lipoprotein (HDL), recombinant soluble LDL receptor 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 an endpoint of infection were
assessed using RT-PCR.
Results
•
r-shLDLR4-292, antibodies against r-shLDLR4-292, and LDL inhibited HCV RNA accumulation
in liver cells, irrespective of genotype or viral load.
•
Inhibition of HCV RNA accumulation
was greatest when r-shLDLR4-292 was present at the time of HCV exposure.
•
Inhibition gradually decreased
as the delay between inoculation and r-shLDLR4-292 treatment increased.
•
In hepatocytes pre-treated
with squalestatin or 25-hydroxycholesterol before HCV exposure, viral RNA accumulation
increased or decreased in parallel with LDL receptor mRNA expression and LDL entry.
Conclusion
In
conclusion, the authors wrote, "LDL receptor is involved at an early stage
in infection of normal human hepatocytes by serum-derived HCV virions."
02/27/07
Reference S
Molina, V Castet, C Fournier-Wirth, and others. The low-density lipoprotein receptor
plays a role in the infection of primary human hepatocytes by hepatitis C virus.
Journal of Hepatology 46(3): 411-419. March 2007.
