Nguyen D H, Liao Z, Buckley J T, Hildreth J E
The Leukocyte Immunochemistry Laboratory, Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Mol Microbiol. 1999 Aug;33(3):659-66. doi: 10.1046/j.1365-2958.1999.01518.x.
Aerolysin is a channel-forming toxin secreted by Aeromonas spp. that binds to glycosyl phosphatidylinositol (GPI)-anchored proteins, such as Thy-1, on sensitive target cells. Receptor binding is followed first by oligomerization of the toxin and then by insertion of the oligomers into the membrane to form stable channels that disrupt the permeability barrier. Human immunodeficiency virus type 1 (HIV-1) produced from T cells is known to incorporate Thy-1 and other GPI-anchored proteins into its membrane. Here, we show that aerolysin is capable of neutralizing HIV-1 in a dose-dependent manner and that neutralization depends upon the presence of these proteins in the viral envelope. Pretreatment with phosphatidylinositol-specific phospholipase C to remove GPI-anchored proteins greatly reduced HIV-1 sensitivity to the toxin, and virus originating from a mutant cell line that lacks GPI-anchored proteins was not neutralized. Aerolysin variants with single amino acid changes that prevent oligomerization or insertion of the toxin were unable to inactivate the virus, implying that channel formation is necessary for neutralization to occur. These findings represent the first evidence that a pathogenic human virus can be neutralized by a bacterial toxin.
气单胞菌溶素是嗜水气单胞菌属分泌的一种成孔毒素，它能与敏感靶细胞上的糖基磷脂酰肌醇（GPI）锚定蛋白（如Thy-1）结合。毒素首先与受体结合，然后发生寡聚化，接着寡聚体插入细胞膜形成稳定的通道，破坏通透性屏障。已知从T细胞产生的1型人类免疫缺陷病毒（HIV-1）会将Thy-1和其他GPI锚定蛋白整合到其膜中。在此，我们表明气单胞菌溶素能够以剂量依赖的方式中和HIV-1，且中和作用取决于病毒包膜中这些蛋白的存在。用磷脂酰肌醇特异性磷脂酶C预处理以去除GPI锚定蛋白，可大大降低HIV-1对该毒素的敏感性，并且源自缺乏GPI锚定蛋白的突变细胞系的病毒未被中和。具有单个氨基酸变化从而阻止毒素寡聚化或插入的气单胞菌溶素变体无法使病毒失活，这意味着通道形成是中和作用发生所必需的。这些发现代表了首个证据，即一种致病性人类病毒可被一种细菌毒素中和。
