Céfai D, Hadida F, Jung M, Debre P, Vernin J G, Seman M
Laboratoire d'Immunologie Cellulaire et Tissulaire, CERVI, La Pitié-Salpêtrière, Paris, France.
AIDS. 1991 Dec;5(12):1453-61. doi: 10.1097/00002030-199112000-00007.
A new Amphotericin B derivative, MS-8209, which retains high antifungal activity with greatly reduced toxicity and improved solubility, has been developed. We investigated the antiviral properties of MS-8209 in Jurkat and CEM T-cell lines and in peripheral blood mononuclear cells infected in vitro with HIV-1BRU. Our results demonstrate, by determination of reverse transcriptase activity and p24 antigen level titration in cell culture supernatants, that MS-8209 inhibits HIV-1 replication in all cell types at concentrations without cytotoxicity. MS-8209 also prevents membrane expression of the HIV-1 large envelope glycoprotein gp120 and the decrease in CD4 level at the surface of infected cells. HIV-1-infected Jurkat cells exhibit a severe signalling defect at CD3 stimulation. Treatment with MS-8209 restores normal responsiveness at CD3 as assessed by measurement of inositol triphosphate accumulation and calcium flux. Finally, our results indicate that MS-8209 inhibits HIV-1BRU replication without preventing virus binding and penetration into target cells.
一种新型两性霉素B衍生物MS-8209已被研发出来，它保留了高抗真菌活性，同时毒性大幅降低且溶解度得到改善。我们研究了MS-8209在Jurkat和CEM T细胞系以及体外感染HIV-1BRU的外周血单核细胞中的抗病毒特性。通过测定细胞培养上清液中的逆转录酶活性和p24抗原水平滴定，我们的结果表明，MS-8209在无细胞毒性的浓度下可抑制所有细胞类型中的HIV-1复制。MS-8209还可防止HIV-1大包膜糖蛋白gp120的膜表达以及受感染细胞表面CD4水平的降低。HIV-1感染的Jurkat细胞在CD3刺激时表现出严重的信号缺陷。通过测量肌醇三磷酸积累和钙通量评估，用MS-8209处理可恢复CD3处的正常反应性。最后，我们的结果表明，MS-8209抑制HIV-1BRU复制，但不阻止病毒与靶细胞的结合和穿透。
