Induction of hepatitis C virus-specific cytotoxic T lymphocytes in mice by an intrahepatic inoculation with an expression plasmid.
We assessed the possibility of intrahepatic inoculation with a plasmid encoding hepatitis C virus (HCV) proteins to elicit HCV-specific cytotoxic T lymphocytes (CTL) in mice as a conventional animal model of HCV infection. BALB/c mice were intrahepatically or intramuscularly inoculated with an expression plasmid DNA encoding HCV structural proteins under the control of the elongation factor 1-alpha promoter. Expressions of HCV-core protein and envelope proteins (E1 and E2) in hepatocytes were detected immunohistochemically 6 days after inoculation. CTL responses were examined using target cells either pulsed with a specific peptide or infected with a recombinant vaccinia virus expressing HCV structural protein. Both intrahepatically and intramuscularly DNA-inoculated mice developed CD8(+), MHC class I-restricted CTL responses that recognized the peptide pulsed as well as HCV proteins expressing target cells. These studies demonstrated the usefulness of a murine model of HCV infection induced by direct intrahepatic DNA inoculation for understanding the immunopathogenic mechanisms in HCV infection.
Kamei
A
A
Department of Bioregulation, Mie University School of Medicine, Mie, 514-8507, Japan.
Tamaki
S
S
Taniyama
H
H
Takamura
S
S
Nishimura
Y
Y
Kagawa
Y
Y
Uno-Furuta
S
S
Kaito
M
M
Kim
G
G
Toda
M
M
Matsuura
Y
Y
Miyamura
T
T
Adachi
Y
Y
Yasutomi
Y
Y
D000818:Animals; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D016174:Hepacivirus / Q000235:genetics / Q000276:immunology*; D018936:Hepatitis C Antigens / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D007150:Immunohistochemistry; D008099:Liver / Q000166:cytology / Q000378:metabolism* / Q000821:virology*; D051379:Mice; D008807:Mice, Inbred BALB C; D020648:Peptide Elongation Factor 1 / Q000235:genetics; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D010957:Plasmids / Q000008:administration & dosage / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics; D013154:Spleen / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D019444:Vaccines, DNA / Q000235:genetics / Q000276:immunology*; D014761:Viral Hepatitis Vaccines / Q000235:genetics / Q000276:immunology; D015678:Viral Structural Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism
D018984:Epitopes, T-Lymphocyte; D018936:Hepatitis C Antigens; D015395:Histocompatibility Antigens Class I; D020648:Peptide Elongation Factor 1; D010446:Peptide Fragments; D019444:Vaccines, DNA; D014761:Viral Hepatitis Vaccines; D015678:Viral Structural Proteins