Levels of N-linked glycosylation on the V1 loop of HIV-1 Env proteins and their relationship to the antigenicity of Env from primary viral isolates

Levels of N-linked glycosylation on the V1 loop of HIV-1 Env proteins and their relationship to the antigenicity of Env from primary viral isolates
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HIV-1 Env 蛋白 V1 环上的 N 连接糖基化水平及其与初级病毒分离株的 Env 抗原性的关系

DOI:
10.2174/157016208785132518
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发表时间:
2008-07-01
影响因子:
1
通讯作者:
Wang, Shixia
Wang, Shixia
中科院分区:
医学4区
文献类型:
--
作者:
Huang, Zuhu;Chou, Arthur;Wang, Shixia

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了解人类免疫缺陷病毒-1(HIV-1)分离株包膜糖蛋白(Env)的结构和功能,对于发展有效的中和抗体应答是有效的HIV-1疫苗的重要组成部分。在本研究中,使用由3价或9价gp120 DNA疫苗配方产生的兔血清,分析了来自不同HIV-1 M组不同分支的一组不同的HIV-1初级包膜病毒的抗原性。三价和九价gp120 DNA疫苗配方都能在免疫的兔子中诱导出HIV-1gp120特异性抗体。然而,我们观察到同一组兔免疫血清具有两种水平的初级包膜抗原性,糖基化水平,特别是在V1环,可能有助于这种多样性。生物信息学分析了N-连接糖基化位点在所有可变区(V1-V5)的分布和平均数目。线性图表明,V1和V4环中潜在的N-糖基化位点的平均数量与环的大小有关。这些数据为HIV-1主要环境抗原的复杂性提供了进一步的证据,并为HIV-1用来逃避保护性免疫反应的机制提供了新的见解。
A good understanding about the structure and function of the envelope glycoprotein (Env) from primary human immunodeficiency virus-1 (HIV-1) isolates is important in facilitating the development of effective neutralizing antibody responses as a component of an effective HIV-1 vaccine. In the current study, the antigenicity of a panel of diverse HIV-1 primary Env from different clades of HIV-1 Group M was analyzed using rabbit sera produced by either 3- or 9-valent gp120 DNA vaccine formulations. Both the 3- and 9-valent gp120 DNA vaccine formulations elicited HIV-1 gp120-specific antibodies in immunized rabbits. However, we observed two levels of primary envelope antigenicity to the same set of rabbit immune sera and that the level of glycosylation, particularly in the V1 loop, may contribute to such diversity. Bioinformatics analysis on the distribution and average number of the N-linked glycosylation sites in all variable regions (V1-V5) was conducted. A linear plot demonstrated that the average number of potential N-glycosylation sites in the V1 and V4 loops correlates to the size of the loop. These data provide further evidence on the complexity of primary HIV-1 Env antigens and offers new insight into the mechanisms that HIV-1 uses to escape protective immune responses.