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嵌合 B/C 重组 HIV-1 包膜糖蛋白 LT5.J4b12C 的膜结合形式的表征。

Characterization of the membrane-bound form of the chimeric, B/C recombinant HIV-1 Env, LT5.J4b12C.

机构信息

1​THSTI-IAVI HIV Vaccine Design Program, Translational Health Science and Technology Institute, Faridabad-121001, Haryana, India.

2​International AIDS Vaccine Initiative, New York, USA.

出版信息

J Gen Virol. 2018 Oct;99(10):1438-1443. doi: 10.1099/jgv.0.001141. Epub 2018 Aug 21.

DOI:10.1099/jgv.0.001141
PMID:30129918
Abstract

Human immunodeficiency virus 1 (HIV-1) diversity is a significant challenge in developing a vaccine against the virus. B/C recombinants have been found in India and other places but are the predominant clade prevalent in China. HIV-1 envelopes (Envs) are the target of broadly neutralizing antibodies (bNAbs) which develop spontaneously in some HIV-1 infected patients. It has been previously reported with efficiently cleaved clade A, B and C Envs that preferential binding of Envs to bNAbs as opposed to non-NAbs, a desirable property for immunogens, is correlated with efficient cleavage of the Env precursor polypeptide into constituent subunits. These Envs are suitable for designing immunogens as soluble proteins, virus-like particles or for delivery by viral vectors/plasmid DNA. However, a B/C recombinant Env with similar properties has not been reported. Here we show that the chimeric, recombinant B/C clade Env LT5.J4b12C is efficiently cleaved on the plasma membrane and selectively binds to bNAbs.

摘要

人类免疫缺陷病毒 1(HIV-1)多样性是开发针对该病毒疫苗的重大挑战。在印度和其他地方发现了 B/C 重组体,但在中国,主要流行的是 B/C 重组体。HIV-1 包膜(Env)是广泛中和抗体(bNAb)的靶标,这些 bNAb 会在一些 HIV-1 感染的患者中自发产生。此前有报道称,对于有效切割的 A、B 和 C Env,Env 与 bNAb 的优先结合,而不是与非 bNAb 的结合,这是免疫原的理想特性,与 Env 前体多肽有效切割成组成亚单位有关。这些 Env 适合设计成可溶性蛋白、病毒样颗粒或通过病毒载体/质粒 DNA 进行递送。然而,尚未报道具有类似特性的 B/C 重组 Env。在这里,我们展示了嵌合的、重组的 B/C 重组体 Env LT5.J4b12C 在质膜上被有效切割,并选择性地与 bNAb 结合。

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引用本文的文献

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Method to identify efficiently cleaved, membrane-bound, functional HIV-1 (Human Immunodeficiency Virus-1) envelopes.高效鉴定经裂解、膜结合的功能性HIV-1(人类免疫缺陷病毒1型)包膜的方法。
MethodsX. 2019 Apr 17;6:837-849. doi: 10.1016/j.mex.2019.04.013. eCollection 2019.