HIV-1 Envelope Glycosylation and the Signal Peptide.

HIV-1 Envelope Glycosylation and the Signal Peptide.
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HIV-1包膜糖基化及其信号肽。

DOI:
10.3390/vaccines9020176
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发表时间:
2021-02-19
期刊:
影响因子:
7.8
通讯作者:
Upadhyay C
Upadhyay C
中科院分区:
医学3区
文献类型:
--
作者:
Lambert GS;Upadhyay C

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相似文献

RV 144试验是唯一一个证明对HIV-1感染有任何保护作用的疫苗试验。虽然这种保护的原因仍在评估中,但它可以作为旨在开发新的,更有效的HIV-1疫苗的广泛努力的理由。我们对HIV-1免疫原和宿主抗体对这些免疫原的反应的了解的进展对于疫苗设计至关重要。虽然包膜(Env)蛋白是病毒粒子表面上存在的唯一病毒蛋白,但它以复杂的三聚体构象存在,并装饰有一系列可变的N-连接聚糖,使其成为疫苗设计的重要但困难的靶标。迄今为止,使用天然Env三聚体的结构模拟物引发保护性体液免疫应答的努力尚未成功。值得注意的是,上述N-连接聚糖作为许多表位的组分,这些表位对于诱导潜在保护性广泛中和抗体(bnAb)至关重要。因此,更好地理解Env结构决定因素,最关键的是Env糖基化,无疑对产生有效的免疫原具有重要意义。最近的研究已经确定HIV-1 Env信号肽(SP)是Env糖基化的重要贡献者。进一步研究SP指导糖基化的机制将是重要的,无论是在理解HIV-1生物学的背景下,为了告知HIV-1疫苗设计。
The RV144 trial represents the only vaccine trial to demonstrate any protective effect against HIV-1 infection. While the reason(s) for this protection are still being evaluated, it serves as justification for widespread efforts aimed at developing new, more effective HIV-1 vaccines. Advances in our knowledge of HIV-1 immunogens and host antibody responses to these immunogens are crucial to informing vaccine design. While the envelope (Env) protein is the only viral protein present on the surface of virions, it exists in a complex trimeric conformation and is decorated with an array of variable N-linked glycans, making it an important but difficult target for vaccine design. Thus far, efforts to elicit a protective humoral immune response using structural mimics of native Env trimers have been unsuccessful. Notably, the aforementioned N-linked glycans serve as a component of many of the epitopes crucial for the induction of potentially protective broadly neutralizing antibodies (bnAbs). Thus, a greater understanding of Env structural determinants, most critically Env glycosylation, will no doubt be of importance in generating effective immunogens. Recent studies have identified the HIV-1 Env signal peptide (SP) as an important contributor to Env glycosylation. Further investigation into the mechanisms by which the SP directs glycosylation will be important, both in the context of understanding HIV-1 biology and in order to inform HIV-1 vaccine design.
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