Low-density Lipoprotein Receptor Plays a Role in HCV Infection of Liver Cells

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.

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.