Virus-Like Particles Carrying HIV-1 Env with a Modulated Glycan Composition

IF 1.5 4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY
G. A. Kaevitser, E. I. Samokhvalov, D. V. Scheblyakov, A. L. Gintsburg, A. N. Vzorov
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引用次数: 0

Abstract

Previously obtained highly immunogenic Env-VLPs ensure overcoming the natural resistance of HIV-1 surface proteins associated with their low level of incorporation and inaccessibility of conserved epitopes to induce neutralizing antibodies. We also adopted this technology to modify Env trimers of the ZM53(T/F) strain to produce Env-VLPs by recombinant vaccinia viruses (rVVs). For VLP production, rVVs expressing Env, Gag-Pol (HIV-1/SIV), and the cowpox virus hr gene, which overcomes the restriction of vaccinia virus replication in CHO cells, were used. The CHO Lec1 engineered cell line lacking GlcNAc-TI was used for generating VLPs with Env proteins containing a cytoplasmic (CT) domain affecting the surface subunit (SU) conformation. This has created the opportunity to modulate the glycan composition, and refine the conditions for their production, and optimize approaches to overcoming HIV-1 resistance associated with abundant glycosylation.

Abstract Image

携带HIV-1 Env的类病毒颗粒,其糖蛋白成分有所改变
以前获得的高免疫原性 Env-VLPs 克服了 HIV-1 表面蛋白的天然抗性,因为它们的结合水平低,而且无法获得保守表位来诱导中和抗体。我们还采用这一技术对 ZM53(T/F) 株的 Env 三聚体进行修饰,通过重组疫苗病毒(rVV)生产 Env-VLP。在生产 VLP 时,使用了表达 Env、Gag-Pol(HIV-1/SIV)和牛痘病毒 hr 基因的 rVVs,该基因克服了疫苗病毒在 CHO 细胞中复制的限制。利用缺乏 GlcNAc-TI 的 CHO Lec1 工程细胞系,生成含有影响表面亚基(SU)构象的胞质(CT)结构域的 Env 蛋白的 VLPs。这为调节糖基组成、改进生产条件以及优化克服与大量糖基化相关的 HIV-1 抗药性的方法提供了机会。
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来源期刊
Molecular Biology
Molecular Biology 生物-生化与分子生物学
CiteScore
1.30
自引率
8.30%
发文量
78
审稿时长
3 months
期刊介绍: Molecular Biology is an international peer reviewed journal that covers a wide scope of problems in molecular, cell and computational biology including genomics, proteomics, bioinformatics, molecular virology and immunology, molecular development biology, molecular evolution and related areals. Molecular Biology publishes reviews, experimental and theoretical works. Every year, the journal publishes special issues devoted to most rapidly developing branches of physical-chemical biology and to the most outstanding scientists.
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