Roche Stéphane, Gaudin Yves
Laboratoire de Virologie Moléculaire et Structurale, CNRS, 91198 Gif sur Yvette Cedex, France.
J Virol. 2004 Aug;78(16):8746-52. doi: 10.1128/JVI.78.16.8746-8752.2004.
Fusion of rabies virus with membranes is triggered at a low pH and is mediated by a viral glycoprotein (G). Fusion of rabies virus with liposomes was monitored by using a lipid mixing assay based on fluorescence resonance energy transfer. Fusion was detected below pH 6.4, and its extent increased with H(+) concentrations to be maximal around pH 6.15. The origin of the partial fusion activity of rabies virus under suboptimal pH conditions (i.e., between pH 6.15 and 6.4) was investigated. We demonstrate unambiguously that fusion at a suboptimal pH is distinct from the phenomenon of low-pH-induced inactivation and that it is not due to heterogeneity of the virus population. We also show that viruses that do not fuse under suboptimal pH conditions are indeed bound to the target liposomes and that the fusion complexes they have formed are blocked at an early stage of the fusion pathway. Our conclusion is that along the fusion reaction, different kinds of fusion machines with different pH thresholds for fusion can be formed. Possible explanations of this difference of pH sensitivity are discussed.
狂犬病病毒与细胞膜的融合在低pH值下被触发，并由病毒糖蛋白（G）介导。通过基于荧光共振能量转移的脂质混合试验监测狂犬病病毒与脂质体的融合。在pH 6.4以下检测到融合，其程度随着H(+)浓度增加，在pH 6.15左右达到最大。研究了狂犬病病毒在非最佳pH条件下（即pH 6.15至6.4之间）部分融合活性的起源。我们明确证明，在非最佳pH值下的融合不同于低pH诱导的失活现象，且它不是由于病毒群体的异质性所致。我们还表明，在非最佳pH条件下不融合的病毒确实与靶脂质体结合，并且它们形成的融合复合物在融合途径的早期阶段被阻断。我们的结论是，沿着融合反应，可以形成具有不同融合pH阈值的不同种类的融合机器。讨论了这种pH敏感性差异的可能解释。
