アクティブボード・２０１２年１２月
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研究発表を行った学会；
・13th Federation of Asian and Oceanian Biochemists and Molecular Biologists (FAOBMB) Congress of Biochemistry and Molecular Biology.
　２０１２年１１月２５日〜２９日（Bangkok）

タイトル；The anti-HIV-1 infection effects of the biscoclaurine alcaloid cepharanthine.

発表者；松田　幸樹　氏
　　　（熊本大学　エイズ学研究センター　岡田プロジェクト研究室）
Abstract；
Membrane fusion between HIV-1 and cells is an essential step for infection. Membrane fluidity is known to affect HIV-1 infection. Cepharanthine (CEP), a biscolaurine alkaloid isolated from Stephania cepharantha Hayata, has been shown to have anti-inflammatory, anti-allergic, and imunomodulatory effects. CEP is widely used for the treatment of patients with various inflammatory diseases in Japan without any serious side effects. It has been reported that CEP inhibited the reproduction process of HIV-1 by inhibition of NF-κB pathway. In this study, we evaluated the effects of CEP on HIV-1 entry process since CEP also has membrane-stabilizing effects.
We analyzed the HIV-1 infection inhibitory effects on PHA-stimulated peripheral blood mononuclear cells (PBMC) by intracellular p24 staining using flow cytometry. Additionally, we measured p24 antigen in cell culture supernatant. HIV-1 infection in PHA-stimulated PBMC was 80 % inhibited by CEP-pretreatment. Next, we co-cultured both inducible Env from X4 HIV-1 expressing T cell lines (JurkatHXBC2 and Jurkat522F/Y) and MOLT-4 T cell line as target cells and evaluated the cell-to-cell fusion inhibitory effects by using flow cytometry and fluorescent microscopy. CEP also blocked the cell-to-cell fusion in a dose-dependent manner. Moreover, we evaluated the differences of the cell membrane fluidity by using fluorescence depolarization assay. CEP decreased fluidity of cell membrane.
Here, we suggest that cell membrane is an important target of viral infection defense. CEP has anti HIV-1 effects since it has dual effects to inhibit NF-κB pathway and HIV-1 entry process by decrease cell membrane fluidity.