Molecular Evolution of HIV-1 CRF01_AE Env in Thai Patients
Molecular Evolution of HIV-1 CRF01_AE Env in Thai Patients
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DOI：
10.1371/journal.pone.0027098
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发表时间：
2011-11-02
期刊：
影响因子：
3.7
通讯作者：
Kameoka, Masanori
中科院分区：
文献类型：
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作者：
Boonchawalit, Samatchaya;Jullaksorn, Duangrat;Kameoka, Masanori
背景资料：包膜糖蛋白（Env）gp 120和gp 41是人类免疫缺陷病毒1型（human immunodeficiency virus type 1，HIV-1）中最具可变性的蛋白质，是抗HIV-1体液免疫应答的主要靶点。HIV-1的一种循环重组形式CRF01_AE在整个东南亚流行;然而，目前关于CRF01_AE Env免疫学特征的信息有限。在这项研究中，我们试图研究CRF 01_AE Env的进化模式下的选择压力的主机immune responses.Methodology/Principal Findings：外周血样本定期收集超过3年的15个HIV-1感染者居住在泰国北部北方，和扩增的env基因的样本进行计算分析。gp 120的V5区域在3年内的几个样品中显示出最高的变异性，而gp 120的V1/V2和/或V4区域在许多样品中也显示出高变异性。此外，在gp 120的保守区域中，gp 120的C3区的N-末端部分显示出最高的氨基酸多样性。在gp 120可变区和潜在的N-连接糖基化（PNLG）位点的氨基酸残基的数量的时间变化参与增加的Env gp 120的可变性。此外，C3区含有几个可能处于正选择下的氨基酸残基，并且在这些残基中经常检测到APOBEC 3家族蛋白介导的G至A突变。有几个因素，包括特别是在gp 120 C3和V5区的氨基酸取代以及PNLG位点数目和gp 120可变区长度的变化，发现参与CRF01_AE Env的分子进化。此外，CRF01_AE和C亚型Env之间在gp 120 V3和C3区的氨基酸变异方面观察到类似的趋势。这些结果可为了解CRF01_AE Env的免疫学特性提供重要信息。
Background: The envelope glycoproteins (Env), gp120 and gp41, are the most variable proteins of human immunodeficiency virus type 1 (HIV-1), and are the major targets of humoral immune responses against HIV-1. A circulating recombinant form of HIV-1, CRF01_AE, is prevalent throughout Southeast Asia; however, only limited information regarding the immunological characteristics of CRF01_AE Env is currently available. In this study, we attempted to examine the evolutionary pattern of CRF01_AE Env under the selection pressure of host immune responses.Methodology/Principal Findings: Peripheral blood samples were collected periodically over 3 years from 15 HIV-1-infected individuals residing in northern Thailand, and amplified env genes from the samples were subjected to computational analysis. The V5 region of gp120 showed highest variability in several samples over 3 years, whereas the V1/V2 and/or V4 regions of gp120 also showed high variability in many samples. In addition, the N-terminal part of the C3 region of gp120 showed highest amino acid diversity among the conserved regions of gp120. Chronological changes in the numbers of amino acid residues in gp120 variable regions and potential N-linked glycosylation (PNLG) sites are involved in increasing the variability of Env gp120. Furthermore, the C3 region contained several amino acid residues potentially under positive selection, and APOBEC3 family protein-mediated G to A mutations were frequently detected in such residues.Conclusions/Significance: Several factors, including amino acid substitutions particularly in gp120 C3 and V5 regions as well as changes in the number of PNLG sites and in the length of gp120 variable regions, were revealed to be involved in the molecular evolution of CRF01_AE Env. In addition, a similar tendency was observed between CRF01_AE and subtype C Env with regard to the amino acid variation of gp120 V3 and C3 regions. These results may provide important information for understanding the immunological characteristics of CRF01_AE Env.