Iron enhances hepatitis C virus replication in cultured human hepatocytes.
BACKGROUND
Iron overload in the presence of increasing concentrations of iron is one of the indicators of poor response to interferon therapy in chronic hepatitis C. In order to analyze the effect of iron on hepatitis C virus (HCV) replication, we measured replication in an HCV-infected cell line.


RESULTS
Cells from a non-neoplastic HCV-infected human hepatocyte line (PH5CH8) susceptible to HCV infection and supportive of HCV replication were used in this study. The replication of HCV RNA was measured by reverse transcription-nested polymerase chain reaction (RT-nested PCR). PH5CH8 cell viability was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. PH5CH8 cells were incubated with 0, 1, 10, 50, and 100 microM of FeSO4 at 37 degrees C with 5% CO2. Forty-eight hours after iron supplementation, the quantity of HCV RNA in the cells incubated in 50 and 100 microM of FeSO4 was approximately ten times that of the cells with no iron supplementation. Similar changes were observed beginning at 12 h from supplementation with FeSO4 and continued for at least 72 h after supplementation. MTT assay indicated that iron did not have cytotoxic effects on the PH5CH8 cells.


CONCLUSIONS
Iron enhances HCV replication in a hepatocyte cell line. The results suggest that iron deposition in hepatocytes could facilitate HCV infection in the liver.
Kakizaki
S
S
The First Department of Internal Medicine, Gunma University School of Medicine, Maebashi, Japan.
Takagi
H
H
Horiguchi
N
N
Toyoda
M
M
Takayama
H
H
Nagamine
T
T
Mori
M
M
Kato
N
N
D002461:Cell Line, Transformed; D002470:Cell Survival / Q000187:drug effects; D004396:Coloring Agents / Q000378:metabolism; D017931:DNA Primers / Q000737:chemistry; D016174:Hepacivirus / Q000187:drug effects / Q000235:genetics / Q000254:growth & development*; D006801:Humans; D007501:Iron / Q000494:pharmacology*; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000821:virology*; D012367:RNA, Viral / Q000032:analysis / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013778:Tetrazolium Salts / Q000378:metabolism; D013844:Thiazoles / Q000378:metabolism; D014779:Virus Replication / Q000187:drug effects / Q000235:genetics
D004396:Coloring Agents; D017931:DNA Primers; D012367:RNA, Viral; D013778:Tetrazolium Salts; D013844:Thiazoles; D007501:Iron; C022616:thiazolyl blue