[Very low-density lipoproteins at HCV targets]
>>Hepatitis C virus production by human hepatocytes dependent on assembly and secretion of very low-density lipoproteins.
Proc Natl Acad Sci U S A. 2007 Apr 3;104(14):5848-53. Epub 2007 Mar 21
Huang H, Sun F, Owen DM, Li W, Chen Y, Gale M Jr, Ye J.
Departments of *Molecular Genetics, Microbiology, and Cell Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9046.
Hepatitis C virus (HCV) and triglyceride-rich very low-density lipoproteins (VLDLs) both are secreted uniquely by hepatocytes and circulate in blood in a complex. Here, we isolated from human hepatoma cells the membrane vesicles in which HCV replicates. These vesicles, which contain the HCV replication complex, are highly enriched in proteins required for VLDL assembly, including apolipoprotein B (apoB), apoE, and microsomal triglyceride transfer protein. In hepatoma cells that constitutively produce infectious HCV, HCV production is reduced by two agents that block VLDL assembly: an inhibitor of microsomal triglyceride transfer protein and siRNA directed against apoB. These results provide a possible explanation for the restriction of HCV production to the liver and suggest new cellular targets for treatment of HCV infection.<<
Full text freebie at PNAS:
pnas.org
Various MTP inhibitors are in development (Aegerion, Surface Logix), but they have long term tox issues, suggesting that this might be a short course of adjunctive therapy. Like claudin-1 mentioned in the previous post, it's a host target, and should have fewer viral resistance issues, though it will probably have some. The target can even be hit with immunologically, as IL-1 modulates the VLDL receptor.
Cheers, Tuck |
