RELATIONSHIP BETWEEN THE INFECTIVITY OF INFLUENZA-VIRUS AND THE ABILITY OF ITS FUSION PEPTIDE TO PERTURB BILAYERS
RELATIONSHIP BETWEEN THE INFECTIVITY OF INFLUENZA-VIRUS AND THE ABILITY OF ITS FUSION PEPTIDE TO PERTURB BILAYERS
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DOI：
10.1006/bbrc.1994.2089
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发表时间：
1994-08-15
影响因子：
3.1
通讯作者：
EPAND, RF
中科院分区：
文献类型：
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作者：
EPAND, RM;EPAND, RF
流感病毒HA2蛋白的氨基末端片段被认为是膜融合的重要区域。我们证明了与HA2蛋白这一区域相对应的模型肽促进倒相形成的能力与完整病毒的融合性之间存在关联。野生型病毒在pH为5时可与膜融合，但在pH为7.4时不能与膜融合。我们发现，在pH为5时，野生型病毒的融合肽降低了双棕榈油酰磷脂酰乙醇胺的双层-六方相变温度，而在pH为7.4时，它提高了该相变温度。此外，已有研究表明，位点特异性突变导致Gly被Glu取代，从而导致病毒感染性的丧失。病毒融合多肽中的这些相同的氨基酸取代导致多肽不再能够降低双层到六方相变温度，即使在酸性pH下也是如此。野生型融合肽促进结构的形成，这些结构在pH为5.0时产生各向同性的P-31核磁共振谱，而在pH为7.4时不产生。与Glu到Gly突变相对应的两个融合肽序列的改变，在酸性pH下不促进各向同性的P-31核磁共振信号。这些结果表明，流感病毒的融合性部分依赖于HA2的氨基末端区域破坏稳定的双层堆积和诱导与倒相结构相对应的曲率应变的能力。(C)1994年学术出版社。
The amino terminal segment of the HA2 protein of influenza virus has been identified as an important region for membrane fusion. We demonstrate that there is an association between the ability of model peptides corresponding to this region of the HA2 protein to promote the formation of inverted phases and the fusogenicity of the intact virus. The wild type virus can fuse to membranes at pH 5 but not at pH 7.4. We show that the fusion peptide of the wild type virus lowers the bilayer to hexagonal phase transition temperature of dipalmitoleoylphosphatidylethanolamine at pH 5 but at pH 7.4 it raises this transition temperature. In addition it has been shown that site specific mutagenesis resulting in the substitution of Gly with Glu leads to a loss of viral infectivity. These same amino acid substitutions in the viral fusion peptide result in the peptide no longer being able to lower the bilayer to hexagonal phase transition temperature, even at acidic pH. The wild type fusion peptide promotes the formation of structures which give rise to isotropic P-31 NMR spectra at pH 5.0 but not at pH 7.4. The two altered sequences of the fusion peptide, corresponding to the Glu to Gly mutations, do not promote isotropic P-31 NMR signals at acidic pH. These results indicate that the fusogenicity of influenza virus is dependent, in part, on the ability of the amino terminal region of HA2 to disrupt stable bilayer packing and to induce curvature strain corresponding to inverted phase structures. (C) 1994 Academic Press, Inc.