Takehara Tetsuo, Suzuki Takahiro, Ohkawa Kazuyoshi, Hosui Atsushi, Jinushi Masahisa, Miyagi Takuya, Tatsumi Tomohide, Kanazawa Yoshiyuki, Hayashi Norio
Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan.
J Hepatol. 2006 Feb;44(2):267-74. doi: 10.1016/j.jhep.2005.07.030. Epub 2005 Aug 25.
BACKGROUND/AIMS: The lack of small animal models supporting chronic hepatitis B virus (HBV) infection impedes the assessment of anti-viral drugs in the whole animal. Although transgenic mice have been used for this purpose, these models are clearly different from natural infection, because HBV is produced from the integrated HBV sequence harbored in all hepatocytes.
Balb/cA nude mice were hydrodynamically injected with a plasmid having 1.5-fold over-length of HBV DNA and analyzed for HBV replication.
Hydrodynamically injected mice showed substantial levels of antigenemia and viremia for more than 1 year. Covalently closed circular DNA (cccDNA), the template of viral replication in natural infection, was produced in the livers and was critically involved in the long-term HBV production, because disruption of the pol gene of the inoculated DNA resulted in transient expression of HBV genes for less than 2 months. Administration of the IFNalpha gene transiently suppressed HBV DNA replication, but was not capable of eliminating HBV in this model.
In vivo gene transfer of a plasmid encoding HBV DNA can establish chronic viral replication in mice, which involves, at least in part, new synthesis of the HBV cccDNA episome, thus recapitulating a part of human HBV infection.
背景/目的：缺乏支持慢性乙型肝炎病毒（HBV）感染的小动物模型阻碍了在整体动物中对抗病毒药物的评估。尽管转基因小鼠已用于此目的，但这些模型与自然感染明显不同，因为HBV是由所有肝细胞中整合的HBV序列产生的。
通过流体动力学方法向Balb/cA裸鼠注射具有1.5倍超长HBV DNA的质粒，并分析HBV复制情况。
通过流体动力学方法注射的小鼠在超过1年的时间里呈现出显著水平的抗原血症和病毒血症。共价闭合环状DNA（cccDNA），即自然感染中病毒复制的模板，在肝脏中产生，并在长期HBV产生中起关键作用，因为接种DNA的pol基因破坏导致HBV基因短暂表达少于2个月。给予IFNα基因可短暂抑制HBV DNA复制，但在此模型中无法消除HBV。
编码HBV DNA的质粒的体内基因转移可在小鼠中建立慢性病毒复制，这至少部分涉及HBV cccDNA附加体的新合成，从而重现了人类HBV感染的一部分情况。
