Chazal N, Singer G, Aiken C, Hammarskjöld M L, Rekosh D
Myles H. Thaler Center for AIDS and Human Retrovirus Research, University of Virginia, Charlottesville, Virginia 22908, USA.
J Virol. 2001 Apr;75(8):4014-8. doi: 10.1128/JVI.75.8.4014-4018.2001.
We have investigated the effects of Nef on infectivity in the context of various viral envelope proteins. These experiments were performed with a minimal vector system where Nef is the only accessory protein present. Our results support the hypothesis that the route of entry influences the ability of Nef to enhance human immunodeficiency virus (HIV) infectivity. We show that HIV particles pseudotyped with Ebola virus glycoprotein or vesicular stomatitis virus glycoprotein (VSV-G), which fuse at low pH, do not require Nef for optimal infectivity. In contrast, Nef significantly enhances the infectivity of virus particles that contain envelope proteins that fuse at neutral pH (CCR5-dependent HIV Env, CXCR4-dependent HIV Env, or amphotropic murine leukemia virus Env). In addition, our results demonstrate that virus particles containing mixed CXCR4-dependent HIV and VSV-G envelope proteins show a conditional requirement for Nef for optimal infectivity, depending on which protein is allowed to facilitate entry.
我们研究了Nef在各种病毒包膜蛋白背景下对感染性的影响。这些实验是在一个最小化载体系统中进行的,其中Nef是唯一存在的辅助蛋白。我们的结果支持这样一种假设,即进入途径会影响Nef增强人类免疫缺陷病毒(HIV)感染性的能力。我们发现,用埃博拉病毒糖蛋白或水泡性口炎病毒糖蛋白(VSV-G)假型化的HIV颗粒在低pH值下融合,其最佳感染性不需要Nef。相反,Nef显著增强了含有在中性pH值下融合的包膜蛋白的病毒颗粒的感染性(CCR5依赖性HIV包膜、CXCR4依赖性HIV包膜或嗜异性小鼠白血病病毒包膜)。此外,我们的结果表明,含有混合的CXCR4依赖性HIV和VSV-G包膜蛋白的病毒颗粒对Nef的最佳感染性有条件需求,这取决于允许哪种蛋白促进进入。