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 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.
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 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.
Authors: Joachim Lupberger; Mirjam B Zeisel; Fei Xiao; Christine Thumann; Isabel Fofana; Laetitia Zona; Christopher Davis; Christopher J Mee; Marine Turek; Sebastian Gorke; Cathy Royer; Benoit Fischer; Muhammad N Zahid; Dimitri Lavillette; Judith Fresquet; François-Loïc Cosset; S Michael Rothenberg; Thomas Pietschmann; Arvind H Patel; Patrick Pessaux; Michel Doffoël; Wolfgang Raffelsberger; Olivier Poch; Jane A McKeating; Laurent Brino; Thomas F Baumert Journal: Nat Med Date: 2011-04-24 Impact factor: 53.440