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乙型肝炎病毒和丙型肝炎病毒在人肝嵌合小鼠中不存在病毒干扰,对干扰素的敏感性也不同。

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

机构信息

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.

出版信息

J Hepatol. 2009 Dec;51(6):1046-54. doi: 10.1016/j.jhep.2009.09.002. Epub 2009 Sep 23.

DOI:10.1016/j.jhep.2009.09.002
PMID:19853955
Abstract

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.

摘要

背景/目的:乙型肝炎病毒(HBV)和丙型肝炎病毒(HCV)均在肝脏内复制,并对固有免疫和干扰素(IFN)治疗产生耐药性。这两种病毒之间是否存在干扰仍存在争议。我们研究了这两种病毒之间的干扰以及对 IFN 产生耐药的模式。

方法

我们在人肝嵌合小鼠中进行了这两种肝炎病毒的单独或联合感染实验。还建立了稳定产生 HBV 的 Huh7 细胞系,并转染了 HCV JFH1 克隆。用 IFN 处理小鼠和细胞系。测量小鼠血清和培养上清液中的病毒水平以及 IFN 刺激基因的信使 RNA 水平。

结果

在体内未观察到两种病毒之间的明显干扰。无论是否感染另一种病毒,IFN 治疗后血清 HBV 仅减少(0.3 个对数),而 HCV 迅速减少。在体外研究中,两种病毒之间没有干扰。IFN 对每种病毒的作用不受另一种病毒的影响。IFN 在培养上清液中对病毒的减少与体内研究相似。

结论

在没有肝炎的情况下,两种肝炎病毒在肝脏中不存在干扰。两种病毒对 IFN 的耐药机制针对 IFN 系统的不同区域。

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