泰国患者中 HIV-1 CRF01_AE 包膜分子进化

Molecular evolution of HIV-1 CRF01_AE Env in Thai patients.

机构信息

Thailand-Japan Research Collaboration Center on Emerging and Re-emerging Infections, Nonthaburi, Thailand.

出版信息

PLoS One. 2011;6(11):e27098. doi: 10.1371/journal.pone.0027098. Epub 2011 Nov 2.

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.

背景

包膜糖蛋白（Env），gp120 和 gp41，是人类免疫缺陷病毒 1 型（HIV-1）中最具变异性的蛋白，也是针对 HIV-1 的体液免疫反应的主要靶标。一种循环重组形式的 HIV-1，CRF01_AE，在整个东南亚地区流行；然而，目前关于 CRF01_AE Env 的免疫特性的信息非常有限。在这项研究中，我们试图研究 CRF01_AE Env 在宿主免疫反应选择压力下的进化模式。

方法/主要发现：从泰国北部居住的 15 名 HIV-1 感染者中定期采集外周血样本，并对样本中的 env 基因进行计算机分析。gp120 的 V5 区在 3 年的多个样本中显示出最高的变异性，而 gp120 的 V1/V2 和/或 V4 区在许多样本中也显示出高变异性。此外，gp120 的 C3 区的 N 端部分在 gp120 的保守区中显示出最高的氨基酸多样性。gp120 可变区的氨基酸残基数量和潜在的 N 连接糖基化（PNLG）位点的变化参与了 Env gp120 变异性的增加。此外，C3 区包含几个潜在的正选择氨基酸残基，并且 APOBEC3 家族蛋白介导的 G 到 A 突变经常在这些残基中检测到。

结论/意义：几种因素，包括 gp120 C3 和 V5 区的氨基酸取代以及 PNLG 位点数量和 gp120 可变区长度的变化，被揭示参与了 CRF01_AE Env 的分子进化。此外，CRF01_AE 与 C 亚型 Env 之间在 gp120 V3 和 C3 区的氨基酸变异方面表现出相似的趋势。这些结果可能为理解 CRF01_AE Env 的免疫特性提供重要信息。