TY - JOUR
T1 - Hepatitis C virus production by human hepatocytes dependent on assembly and secretion of very low-density lipoproteins
AU - Huang, Hua
AU - Sun, Fang
AU - Owen, David M.
AU - Li, Weiping
AU - Chen, Yan
AU - Gale, Michael
AU - Ye, Jin
PY - 2007/4/3
Y1 - 2007/4/3
N2 - 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.
AB - 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.
KW - Apolipoprotein B
KW - Microsomal triglyceride transfer protein
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U2 - 10.1073/pnas.0700760104
DO - 10.1073/pnas.0700760104
M3 - Article
C2 - 17376867
AN - SCOPUS:34250337631
SN - 0027-8424
VL - 104
SP - 5848
EP - 5853
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 14
ER -