Hepatitis C virus production by human hepatocytes dependent on assembly and secretion of very low-density lipoproteins.
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.
Huang
Hua
H
Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, TX 75390-9046, USA.
Sun
Fang
F
Owen
David M
DM
Li
Weiping
W
Chen
Yan
Y
Gale
Michael
M
Ye
Jin
J
D001055:Apolipoproteins B / Q000378:metabolism; D001057:Apolipoproteins E / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000473:pathology; D045744:Cell Line, Tumor; D016174:Hepacivirus / Q000235:genetics / Q000378:metabolism*; D022781:Hepatocytes / Q000821:virology*; D006801:Humans; D018189:Immunomagnetic Separation; D008079:Lipoproteins, VLDL / Q000378:metabolism*; D008113:Liver Neoplasms / Q000473:pathology; D008861:Microsomes / Q000737:chemistry / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism / Q000494:pharmacology; D012093:Replicon; D014280:Triglycerides / Q000037:antagonists & inhibitors
D001055:Apolipoproteins B; D001057:Apolipoproteins E; D008079:Lipoproteins, VLDL; D034741:RNA, Small Interfering; D014280:Triglycerides