B型肝炎ウイルス(HBV)の感染により発症する慢性B型肝炎は, 肝癌や肝硬変のリスク因子である。現在の治療薬は核酸アナログとインターフェロンのみであり, ウイルスを排除できないことが問題である。そこで本研究では, HBV感染の構造メカニズムを明らかにし, 治療薬創製の構造基盤を得ることを目指した。
感染に重要なHBVの外殻タンパク質であるpreS, preS1, preS2の大量調製法を確立し, NMRシグナルの帰属を行うことで, HBV受容体であるNTCPとの相互作用解析の準備が整った。NTCPは大腸菌での発現に成功した。
Chronic hepatitis B is a global health problem caused by the hepatitis B virus (HBV) infection, which leads to liver cancer and liver cirrhosis. There are two types of drugs for the treatment of HBV infection : nucleotide analogue and interferon. However, these drugs can hardly eliminate HBV completely from the infected cells. Aim of this study was to obtain structural basis for HBV infection useful for the treatment of HBV infection.
The preS, preS1, and preS2 regions of the surface protein of HBV, which are important for infection, were prepared in large quantities for structural analyses. Assignments of NMR signals derived from preS, preS1, and preS2 were successfully established, which can be used for residue specific analyses of the interaction with NTCP, the HBV receptor specifically expressed in liver. After the examination of some expression vectors, E. coli expression of NTCP was achieved.
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