A novel immunocompetent rat model of HCV infection and hepatitis.
OBJECTIVE
Hepatitis C virus (HCV) infects millions of people worldwide. Therapy is limited, and treatment does not produce a sustained response in the majority of patients. Development of new agents has been hampered by the lack of a convenient animal model. The aim of this study was to determine whether an immunocompetent rat, tolerized and transplanted with a human hepatoma cell line (Huh 7 cells), could be used to sustain an HCV infection.


METHODS
Fetal rats were tolerized in utero with 10(5) Huh 7 cells. One day after birth, rats were transplanted with 5 x 10(6) Huh 7 cells and, a week later, inoculated with HCV, genotype 1.


RESULTS
In tolerized, transplanted, and HCV-infected rats, Huh 7 cells were found in the liver, and HCV viral replication was detected by the presence of negative strand HCV RNA. HCV levels in serum were measured at 11,000 copies/mL at week 4, peaked at 22,500 copies/mL by week 12. In tolerized, transplanted, inoculated rats, but not controls, serum alanine aminotransferase (ALT) values increased to 60 IU/L by week 4 and reached a peak of approximately 120 IU/L by week 13. Histology showed foci of mononuclear infiltrates in portal and central regions.


CONCLUSIONS
HCV-inoculated immunocompetent rats tolerized and transplanted with Huh 7 cells support HCV gene expression, viral replication, and develop biochemical and histologic evidence of hepatitis.
Wu
George Y
GY
Department of Medicine, Division of Gastroenterology-Hepatology, University of Connecticut Health Center, Farmington 06030-1845, USA. wu@nso.uchc.edu
Konishi
Masayoshi
M
Walton
Cherie M
CM
Olive
Denise
D
Hayashi
Kazuhiko
K
Wu
Catherine H
CH
D000818:Animals; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D005260:Female; D016174:Hepacivirus / Q000235:genetics* / Q000302:isolation & purification; D019698:Hepatitis C, Chronic / Q000276:immunology* / Q000503:physiopathology*; D018197:Hepatoblastoma; D007121:Immunocompetence; D008113:Liver Neoplasms; D009368:Neoplasm Transplantation; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D017361:Viral Nonstructural Proteins / Q000235:genetics; D012324:RNA-Dependent RNA Polymerase
D017361:Viral Nonstructural Proteins; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase