Pol I-transcribed hepatitis C virus genome RNA replicates, produces an infectious virus and leads to severe hepatic steatosis in transgenic mice.

作者: Mohammod Johirul ISLAM , Keisuke HIKOSAKA , Hidenao NORITAKE , Mohammad Khaja Mafij UDDIN , Mohammed Badrul AMIN

DOI: 10.2220/BIOMEDRES.36.159

关键词: SteatosisHepatitis C virusHepatocellular carcinomaVirologyGenetically modified mouseRNATransgeneRNA polymerase ILiver diseaseBiology

摘要: Patients chronically infected with hepatitis C virus (HCV) are at risk of developing end-stage liver disease and hepatocellular carcinoma. Development drugs to inhibit hepatocyte damage a vaccine against HCV is hampered by the lack small animal model. We generated mice in which viral genome RNA was always present hepatocytes using special transgene. Here we show that transcribed Pol I polymerase can replicate produce infectious viruses mice. obtained transgenic mouse 200 copies per haploid named A line mouse. It produced ~ 3 × 10(6) copies/mL serum, comparable level as patients chronic infection. This immunotolerant showed hepatic steatosis without any necroinflammation age 6 months or carcinoma 15 months. Thus, be used an model for will enable better study abnormalities metabolism signal transduction hepatocytes, development cure abnormalities.

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