Robinson W E, McDougall B, Tran D, Selsted M E
Department of Pathology, University of California, Irvine 92697-4800, USA.
J Leukoc Biol. 1998 Jan;63(1):94-100. doi: 10.1002/jlb.63.1.94.
Indolicidin is a tridecapeptide amide isolated from the cytoplasmic granules of bovine neutrophils. It has potent, broad spectrum microbicidal activities in vitro that are thought to be related to the membrane-disruptive properties of the peptide. Based on the putative membrane-targeted mode of action, we postulated that indolicidin would be active against HIV-1, an enveloped virus. Indolicidin was reproducibly virucidal against HIV-1 at a concentration of 333 microg/mL (174 microM) with a 50% inhibitory dose between 67 and 100 microg/mL. At 37 degrees C, killing was rapid with >50% killing of HIV occurring within 5 min, and nearly 100% viral inactivation achieved by 60 min. The anti-HIV activity of indolicidin was temperature-sensitive, a finding consistent with a membrane-mediated antiviral mechanism. Parallel experiments revealed that indolicidin lysed cultured lymphoblastoid cells at concentrations similar to those required for antiviral activity. However, a des-R13-amide indolicidin analog (R12-OH), previously shown to have less antibacterial activity than indolicidin, was significantly less active against HIV and was non-toxic to lymphoid target cells at concentrations up to 333 microg/mL, the highest level tested.
吲哚杀菌素是一种从牛嗜中性粒细胞的胞质颗粒中分离出的十三肽酰胺。它在体外具有强大的广谱杀菌活性，这种活性被认为与该肽的膜破坏特性有关。基于假定的膜靶向作用模式，我们推测吲哚杀菌素对包膜病毒HIV-1具有活性。吲哚杀菌素在浓度为333μg/mL（174μM）时对HIV-1具有可重复的杀病毒作用，半数抑制浓度在67至100μg/mL之间。在37℃时，杀灭迅速，5分钟内HIV的杀灭率超过50%，60分钟时几乎实现100%的病毒灭活。吲哚杀菌素的抗HIV活性对温度敏感，这一发现与膜介导的抗病毒机制一致。平行实验表明，吲哚杀菌素在与抗病毒活性所需浓度相似的情况下可裂解培养的淋巴母细胞。然而，一种去-R13-酰胺吲哚杀菌素类似物（R12-OH），此前已证明其抗菌活性低于吲哚杀菌素，对HIV的活性明显较低，并且在高达333μg/mL（测试的最高水平）的浓度下对淋巴靶细胞无毒。
