Absence of viral interference and different susceptibility to interferon between hepatitis B virus and hepatitis C virus in human hepatocyte chimeric mice

Hiraga Nobuhiko

Imamura Michio

Hatakeyama Tsuyoshi

Kitamura Shosuke

Mitsui Fukiko

Tanaka Shinji

Tsuge Masataka

Takahashi Shoichi

Abe Hiromi

Maekawa Toshiro

Ochi Hidenori

Tateno Chise

Yoshizato Katsutoshi

Wakita Takaji

Chayama Kazuaki

Journal of Hepatology

Background/Aims: 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 ill 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 ill 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 ill 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.

Superinfection

JFH-1

IFN-stimulated genes

Medical sciences [ 490 ]

eng

Elsevier Science Bv

Copyright (c) 2009 European Association for the Study of the Liver. Published by Elsevier B.V.

[ISSN] 0168-8278

[DOI] 10.1016/j.jhep.2009.09.002

[NCID] AA10459105

[DOI] http://dx.doi.org/10.1016/j.jhep.2009.09.002