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Preliminary Research To The Effect Of Interferon Induced Transmembrane Protein Molecules Against Hepatitis B Virus

Posted on:2012-10-14Degree:MasterType:Thesis
Country:ChinaCandidate:D D LiFull Text:PDF
GTID:2154330335481098Subject:Biochemistry and Molecular Biology
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Interferon is a kind of small molecule protein owning various biological functions for regulating cell growth, differentiation, immune response, antitumor, and antiviral numerous. It has already been widely used in the prevention and treatment of virus infection and other diseases.It fulfills it's many biological function through a series of interferon induced proteins. Interferon across the membrane protein family (IFN) can be efficiently induced by IFN-α.These protein family is highly similarity in structure and is evolutionary conservative gene, Locatting in human's eleven Chromosome. Human express only IFITM1, IFITM2, IFITM3 and IFITM5,and the top three are widely expression in the liver and so on many other kinds of human tissues. But IFITM5 expresses only in osteoblasts.It contains IFITM6 and IFITM7 in mice with human gene in addition to the above four homologous genes. Besides the human and mouse also has a fake gene IFITM4p. With the deeply activity study of IFITMs for anti-IAV,DFV,VSV,WNV,MARV,EBOV,SARS and HIV in recent years,it has been the star molecule of antiviral natural immune response because of the unique inhibiting virus ability and certain broad-spectrum antiviral activity. But there are not reports in the literature that IFITMs protein molecules are related with hepatitis b virus. To investigate whether the IFITMs has similar role of ant-HBV, we made the following research work:Firstly, we conducted pharmacodynamics experiment of IFITMs protein family for anti-hepatitis b virus in HepG2 cells and mice.We find that IFITM1, IFITM2 and IFITM3 can significantly inhibit the expression of HBeAg and HBsAg and the synthesis of DNA HBV in the cell model of instantaneous to carry PHBV1.31,and IFITM2 and IFITM3 have the most effect significant.Also we find that IFITM3 can significantly reduce the level of HBsAg and HBeAg in the mouse infected C hepatitis b virus. The above experiments proved that IFITMs protein family molecular own the active of anti-HBV replication, especially the IFITM3.Secondly , We explore the mechanism of IFITMs for anti-HBV by HBV report gene experiment and find IFITMs molecules can inhibit report gene expression. These results suggest that the mechanism of inhibiting HBV gene expression could mostly be realized by inhibiting HBV each promoter transcription activity. In addition, we find across the membrane structure domain I is very important in anti-HBV of the IFITM3 protein that the method of missing mutants.As a kind of transmembrane protein molecules,IFITM3 attractes my attention to inhibitory activity to exercise gene transcription. We established a method to find the Interaction molecules targetting to markered protein based on Avi - meta technology.The results show that we have successfully established the biotin generalized markup, purificy and test methods based on Avi - meta technology,which can provide effectively identification technology Because of its high affinity and sensitivity.In summary, preliminary results show that the IFITM3 protein are more effective to inhibition of the replication of hepatitis B virus in vivo and in vitro. This result will provide a new reference and tips for further elucidating the interaction between hepatitis B virus and the host as well as the treatment of patients with hepatitis B virus .
Keywords/Search Tags:interferon, IFITMs protein family, hepatitis B virus
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