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 replicat...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2007-04, Vol.104 (14), p.5848-5853
Main Authors: Huang, Hua, Sun, Fang, Owen, David M, Li, Weiping, Chen, Yan, Gale, Michael Jr, Ye, Jin
Format: Article
Language:English
Subjects:
Antibodies
Apolipoproteins B - metabolism
Apolipoproteins E - metabolism
Biological Sciences
Carcinoma, Hepatocellular - pathology
Cell Line, Tumor
Cell lines
Cells
Cellular immunity
Epitopes
Hepacivirus - genetics
Hepacivirus - metabolism
Hepatitis
Hepatitis C
Hepatitis C virus
Hepatocytes
Hepatocytes - virology
Humans
Immunomagnetic Separation
Lipoproteins, VLDL - secretion
Liver
Liver Neoplasms - pathology
Low density lipoprotein
Microsomes - chemistry
Microsomes - metabolism
Polymerase chain reaction
Replicon
RNA
RNA, Small Interfering - metabolism
RNA, Small Interfering - pharmacology
Secretion
Small interfering RNA
Triglycerides - antagonists & inhibitors
Viruses
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Description
Summary: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.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.0700760104