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DOI: 10.1055/s-0031-1295901
Hepatitis B virus surface proteins induce interferon response in the liver of HBV-transgenic mouse
Chronic hepatitis B virus (HBV) infection is associated with acute and chronic hepatitis, cirrhosis, and hepatocellular carcinoma. Interferon production is induced in host cells in response to pathogens: viruses, bacteria, parasites. Here we analysed transgenic mice (Tg) on two different genetic backgrounds (C57BL/6 and BALB/c) that overproduce the HBV surface proteins in the liver. This model allows studying liver disease that mimics many of the pathological events in humans upon HBV infection1. The aim of this study was to compare the hepatic gene expression of HBV-Tg on two different genetic backgrounds.
Methods: RNA was isolated from the whole liver of 12-weeks-old Tg (C57BL/6 versus BALB/c) mice producing HBV surface proteins and their non-transgenic littermates, labelled and hybridized to whole mouse genome 44 k microarrays (Agilent Technologies). The results obtained by microarray analysis were validated by real-time (RT) PCR. Protein expression and modification was studied by Western blot analysis of whole liver extracts using specific antibodies. Results: Microarray analysis of the whole liver RNA revealed strong regulation of gene expression in the liver of Tg mice compared to littermates. Most interesting, the genes involved in interferon response were up-regulated in the liver of Tg (BALB/c) mice compared to littermates. In contrast, these genes were not regulated in Tg (C57BL/6). Western blot analysis showed up-regulation not only on mRNA but also on protein level. Conclusions: 1. Expression of HBV surface proteins induces interferon response in the liver of HBV-Tg mice. 2. Interferon response induction is mouse strain specific. 3. Possible induction of interferon response could affect the pathological events upon HBV infection.
Literatur: 1. Chisari FV, Filippi P, McLachlan A, Milich DR, Riggs M, Lee S, Palmiter RD, Pinkert CA, Brinster RL. Expression of hepatitis B virus large envelope polypeptide inhibits hepatitis B surface antigen secretion in transgenic mice. J Virol.1986, 60(3):880-887.