Waheed Abdul A, Ablan Sherimay D, Soheilian Ferri, Nagashima Kunio, Ono Akira, Schaffner Carl P, Freed Eric O
Virus-Cell Interaction Section, HIV Drug Resistance Program, NCI-Frederick, Bldg. 535, Rm. 108, Frederick, MD 21702-1201, USA.
J Virol. 2008 Oct;82(19):9776-81. doi: 10.1128/JVI.00917-08. Epub 2008 Jul 23.
We investigated the mechanism by which the cholesterol-binding compound amphotericin B methyl ester (AME) inhibits human immunodeficiency virus type 1 (HIV-1) particle production. We observed no significant effect of AME on Gag binding to the plasma membrane, Gag association with lipid rafts, or Gag multimerization, indicating that the mechanism of inhibition by AME is distinct from that by cholesterol depletion. Electron microscopy analysis indicated that AME significantly disrupts virion morphology. Interestingly, we found that AME does not inhibit the release of Vpu-defective HIV-1 or Vpu(-) retroviruses such as murine leukemia virus and simian immunodeficiency virus. We demonstrated that the ability of Vpu to counter the activity of CD317/BST-2/tetherin is markedly reduced by AME. These results indicate that AME interferes with the anti-CD317/BST-2/tetherin function of Vpu.
我们研究了胆固醇结合化合物两性霉素B甲酯(AME)抑制1型人类免疫缺陷病毒(HIV-1)颗粒产生的机制。我们观察到AME对Gag与质膜的结合、Gag与脂筏的缔合或Gag多聚化均无显著影响,这表明AME的抑制机制与胆固醇耗竭的机制不同。电子显微镜分析表明,AME显著破坏病毒体形态。有趣的是,我们发现AME并不抑制Vpu缺陷型HIV-1或Vpu(-)逆转录病毒(如鼠白血病病毒和猴免疫缺陷病毒)的释放。我们证明,AME可显著降低Vpu对抗CD317/BST-2/栓系蛋白活性的能力。这些结果表明,AME干扰了Vpu的抗CD317/BST-2/栓系蛋白功能。