HIV重组毒株变异对包膜蛋白膜融合功能的影响

HIV Recombinant strains is predominant in China, however, the mechanism of host cells infection by recombinant strains has rarely been studied. Membrane fusion is one of the key steps in the process of HIV infection. Effects of recombinant strain variation on the membrane fusion process, has important scientific significance to reveal the mechanism of membrane fusion. We analyzed Env mediated cell fusion ability of HIV strains, and found that the difference of fusion ability existed not only between inter-subtypes, but also within the same subtype. In this study, the influence of HIV recombinants variation on the fusion activity, cell infection ability, env protein expression and processing level and the affinity of the receptors, and 6-hb structure characteristics will be investigated. Meanwhile, by comparing amino acid sequence of recombinant strains of different fusion ability, constructing pseudotyped HIV mutant virus and identification of fusion related sites or motifs, we expect to clarify the molecular mechanism of how the site variation is to influence the process of membrane fusion.

HIV重组亚型毒株在我国流行极为广泛，然而针对重组毒株细胞感染机制的研究鲜有报道。膜融合是HIV感染宿主细胞过程中关键步骤之一。研究重组毒株遗传变异对膜融合过程的影响，对揭示膜融合机制具有重要的科学意义。我们在分析HIV Env蛋白介导细胞融合能力时，发现膜融合能力强弱不仅存在于亚型间，而且同一亚型内不同毒株也表现出显著的差异。基于上述研究，本课题以重组毒株为对象，研究其遗传变异对病毒膜融合活性、细胞感染能力、ENV蛋白表达和加工水平以及受体亲和力、6-HB结构特征等膜融合过程中关键环节的影响；通过比对不同膜融合能力重组毒株氨基酸序列的差异，并构建假病毒突变株，鉴定膜融合关键位点或结构域，以期阐明位点的变异是如何影响膜融合过程这一分子机制。