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首页> 外文期刊>AIDS Research and Human Retroviruses >Effects of stabilization of the gp41 cytoplasmic domain on fusion activity and infectivity of SIVmac239.
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Effects of stabilization of the gp41 cytoplasmic domain on fusion activity and infectivity of SIVmac239.

机译：gp41胞质域的稳定化对SIVmac239融合活性和感染性的影响。

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摘要

We investigated the effects of introducing specific sequences that are predicted to affect trimer stability into the CT domain of the SIV Env protein. Two constructs, 3HBai and 3HBaa, with additional GCN4-related sequences in the CT domain (45 aa) had enhanced infectivity, and differed in their fusion activity and trimer stability. Another construct, 3HBii, exhibited a very stable trimeric structure. Pseudotyped virions containing 3HBii retained infectivity despite the lack of syncytia formation. In contrast, 3HBai and 3HBaa, which caused extensive syncytia formation, had a less stable trimeric structure. We observed an inverse correlation between trimer stability and fusion activity but no correlation between syncytia formation activity and infectivity. Quantitative cell-cell fusion assays, analysis of Env incorporation, measurement of ectodomain conformation by CD4 binding, and CCR5 blocking assays indicated differential effects on fusion activity and infectivity of the viruses with Env CT modifications. Differences in interaction with CD4 were not affected by trimer stability and were not related to fusion activity or infectivity. The results indicate that changes in the stability of the CT domain can have significant effects on functional activities of the Env external domain and can impact viral biological properties.
机译：我们调查了将可影响三聚体稳定性的特定序列引入SIV Env蛋白的CT域的影响。两个构建体3HBai和3HBaa，在CT域（45aa）中具有额外的GCN4相关序列，具有增强的感染力，并且其融合活性和三聚体稳定性不同。另一构建体3HBii显示出非常稳定的三聚体结构。尽管缺乏合胞体形成，但含有3HBii的假型病毒体仍具有感染力。相反，引起大量合胞体形成的3HBai和3HBaa具有较不稳定的三聚体结构。我们观察到三聚体稳定性和融合活性之间呈负相关，而合胞体形成活性和感染性之间无相关性。定量细胞-细胞融合测定，Env掺入分析，通过CD4结合测量胞外域构象以及CCR5阻断测定均表明，对具有Env CT修饰的病毒的融合活性和感染性有不同的影响。与CD4相互作用的差异不受三聚体稳定性的影响，并且与融合活性或感染性无关。结果表明，CT结构域稳定性的变化可能对Env外部结构域的功能活性产生重大影响，并可能影响病毒的生物学特性。

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