有效切割的HIV-1包膜(Envs)的肯尼迪表位(KE)依赖性逆转录转运及其对Env细胞表面表达和病毒颗粒形成的影响。

IF 1.9 4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY
Supratik Das, Hilal Ahmad Parray, Adarsh Kumar Chiranjivi, Prince Kumar, Abhishek Goswami, Manish Bansal, Deepak Kumar Rathore, Rajesh Kumar, Sweety Samal
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引用次数: 0

摘要

高效切割的HIV-1Env是功能性Env最接近的模拟物,因为它们只特异性暴露bNAb(广泛中和抗体)表位,而不是非中和表位,使其适合开发疫苗免疫原。我们之前已经从分支A、B、C和B/C中鉴定了几种有效切割的Env。我们还描述了这些Env的一个子集的CT(C末端尾部)的截短,而不是其他Env的截短,以CT保守亲水结构域(CHD)或肯尼迪表位(KE)依赖的方式损害了它们在细胞表面的胞外结构域构象/抗原性。在这里,我们报告那些Env(4 - 2.J41和JRCSF),其在细胞表面上的天然样外结构域构象/抗原性在CT截短时被破坏,而不是其他Env如JRFL,其CT截短对细胞表面上外结构域完整性没有影响,其在从早期到晚期内体的逆行转运中也有缺陷。这些Env的CT中CHD/KE的恢复恢复了早期和晚期内体之间的野生型分布水平。在存在逆行转运抑制剂Retro 2的情况下,4 - 2.J41和JRCSF Envs增加[在存在Rab7a DN和Rab7b DN(DN:显性阴性)的情况下也是如此],但颗粒形成减少4 - 2.J41和JRCSF Env假型病毒。我们的结果首次显示了CT依赖性、CHD/KE调节的逆行转运与这些有效切割的Env的细胞表面表达/病毒颗粒形成之间的相关性。基于我们的结果,我们假设这些有效切割的Env的一个子集使用CT依赖性、CHD/KE介导的机制来组装和从晚期内体释放。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Kennedy Epitope (KE)-dependent Retrograde Transport of Efficiently Cleaved HIV-1 Envelopes (Envs) and its Effect on Env Cell Surface Expression and Viral Particle Formation

Kennedy Epitope (KE)-dependent Retrograde Transport of Efficiently Cleaved HIV-1 Envelopes (Envs) and its Effect on Env Cell Surface Expression and Viral Particle Formation

Kennedy Epitope (KE)-dependent Retrograde Transport of Efficiently Cleaved HIV-1 Envelopes (Envs) and its Effect on Env Cell Surface Expression and Viral Particle Formation

Efficiently cleaved HIV-1 Envs are the closest mimics of functional Envs as they specifically expose only bNAb (broadly neutralizing antibody) epitopes and not non-neutralizing ones, making them suitable for developing vaccine immunogens. We have previously identified several efficiently cleaved Envs from clades A, B, C and B/C. We also described that truncation of the CT (C-terminal tail) of a subset of these Envs, but not others, impairs their ectodomain conformation/antigenicity on the cell surface in a CT conserved hydrophilic domain (CHD) or Kennedy epitope (KE)-dependent manner. Here, we report that those Envs (4 − 2.J41 and JRCSF), whose native-like ectodomain conformation/antigenicity on the cell surface is disrupted upon CT truncation, but not other Envs like JRFL, whose CT truncation does not have an effect on ectodomain integrity on the cell surface, are also defective in retrograde transport from early to late endosomes. Restoration of the CHD/KE in the CT of these Envs restores wild-type levels of distribution between early and late endosomes. In the presence of retrograde transport inhibitor Retro 2, cell surface expression of 4 − 2.J41 and JRCSF Envs increases [as does in the presence of Rab7a DN and Rab7b DN (DN: dominant negative)] but particle formation decreases for 4 − 2.J41 and JRCSF Env pseudotyped viruses. Our results show for the first time a correlation between CT-dependent, CHD/KE regulated retrograde transport and cell surface expression/viral particle formation of these efficiently cleaved Envs. Based on our results we hypothesize that a subset of these efficiently cleaved Envs use a CT-dependent, CHD/KE-mediated mechanism for assembly and release from late endosomes.

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来源期刊
The Protein Journal
The Protein Journal 生物-生化与分子生物学
CiteScore
5.20
自引率
0.00%
发文量
57
审稿时长
12 months
期刊介绍: The Protein Journal (formerly the Journal of Protein Chemistry) publishes original research work on all aspects of proteins and peptides. These include studies concerned with covalent or three-dimensional structure determination (X-ray, NMR, cryoEM, EPR/ESR, optical methods, etc.), computational aspects of protein structure and function, protein folding and misfolding, assembly, genetics, evolution, proteomics, molecular biology, protein engineering, protein nanotechnology, protein purification and analysis and peptide synthesis, as well as the elucidation and interpretation of the molecular bases of biological activities of proteins and peptides. We accept original research papers, reviews, mini-reviews, hypotheses, opinion papers, and letters to the editor.
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