Absence of viral interference and different susceptibility to interferon between hepatitis B virus and hepatitis C virus in human hepatocyte chimeric mice.
OBJECTIVE
Both hepatitis B virus (HBV) and hepatitis C virus (HCV) replicate in the liver and show resistance against innate immunity and interferon (IFN) treatment. Whether there is interference between these two viruses is still controversial. We investigated the interference between these two viruses and the mode of resistance against IFN.


METHODS
We performed infection experiments with either or both of the two hepatitis viruses in human hepatocyte chimeric mice. Huh7 cell lines with stable production of HBV were also established and transfected with HCV JFH1 clone. Mice and cell lines were treated with IFN. The viral levels in mice sera and culture supernatants and messenger RNA levels of IFN-stimulated genes were measured.


RESULTS
No apparent interference between the two viruses was seen in vivo. Only a small (0.3 log) reduction in serum HBV and a rapid reduction in HCV were observed after IFN treatment, regardless of infection with the other virus. In in vitro studies, no interference between the two viruses was observed. The effect of IFN on each virus was not affected by the presence of the other virus. IFN-induced reductions of viruses in culture supernatants were similar to those in in vivo study.


CONCLUSIONS
No interference between the two hepatitis viruses exists in the liver in the absence of hepatitis. The mechanisms of IFN resistance of the two viruses target different areas of the IFN system.
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, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan.
Imamura
Michio
M
Hatakeyama
Tsuyoshi
T
Kitamura
Shosuke
S
Mitsui
Fukiko
F
Tanaka
Shinji
S
Tsuge
Masataka
M
Takahashi
Shoichi
S
Abe
Hiromi
H
Maekawa
Toshiro
T
Ochi
Hidenori
H
Tateno
Chise
C
Yoshizato
Katsutoshi
K
Wakita
Takaji
T
Chayama
Kazuaki
K
D000818:Animals; D002460:Cell Line; D016174:Hepacivirus / Q000187:drug effects / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D006515:Hepatitis B virus / Q000187:drug effects / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D022781:Hepatocytes / Q000187:drug effects / Q000276:immunology* / Q000637:transplantation / Q000821:virology*; D006801:Humans; D007113:Immunity, Innate; D066298:In Vitro Techniques; D007370:Interferon Type I / Q000494:pharmacology*; D051379:Mice; D016513:Mice, SCID; D011994:Recombinant Proteins; D014162:Transfection; D018183:Transplantation Chimera; D014183:Transplantation, Heterologous; D014762:Viral Interference / Q000276:immunology*; D019562:Viral Load / Q000187:drug effects; D014779:Virus Replication / Q000187:drug effects / Q000276:immunology
D007370:Interferon Type I; D011994:Recombinant Proteins