Infection of human hepatocyte chimeric mouse with genetically engineered hepatitis C virus and its susceptibility to interferon.
We developed a reverse genetics system of hepatitis C virus (HCV) genotypes 1a and 2a using infectious clones and human hepatocyte chimeric mice. We inoculated cell culture-produced genotype 2a (JFH-1) HCV intravenously. We also injected genotype 1a CV-H77C clone RNA intrahepatically. Mice inoculated with HCV by both procedures developed measurable and transmissible viremia. Interferon (IFN) alpha treatment resulted in greater reduction of genotype 2a HCV levels than genotype 1a, as seen in clinical practice. Genetically engineered HCV infection system should be useful for analysis of the mechanisms of resistance of HCV to IFN and other drugs.
Hiraga
Nobuhiko
N
Department of Medicine and Molecular Science, Division of Frontier Medical Science, Programs for Biomedical Research, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan.
Imamura
Michio
M
Tsuge
Masataka
M
Noguchi
Chiemi
C
Takahashi
Shoichi
S
Iwao
Eiji
E
Fujimoto
Yoshifumi
Y
Abe
Hiromi
H
Maekawa
Toshiro
T
Ochi
Hidenori
H
Tateno
Chise
C
Yoshizato
Katsutoshi
K
Sakai
Akihito
A
Sakai
Yoshio
Y
Honda
Masao
M
Kaneko
Shuichi
S
Wakita
Takaji
T
Chayama
Kazuaki
K
D000818:Animals; D002478:Cells, Cultured; D002678:Chimera / Q000821:virology*; D002999:Clone Cells; D005818:Genetic Engineering; D005838:Genotype; D016174:Hepacivirus / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D006526:Hepatitis C / Q000821:virology*; D022781:Hepatocytes / Q000187:drug effects / Q000637:transplantation* / Q000821:virology*; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology*; D051379:Mice; D012367:RNA, Viral / Q000097:blood; D012692:Serial Passage; D012709:Serum Albumin; D014158:Transcription, Genetic / Q000187:drug effects; D019562:Viral Load
D016898:Interferon-alpha; D012367:RNA, Viral; D012709:Serum Albumin