Association of envelope-specific B-cell differentiation and viral selective pressure signatures in HIV-1 CRF01

DOI：

10.1097/qad.0000000000003323

发表时间：

2022-10-01

期刊：

AIDS

影响因子：

3.8

通讯作者：

中科院分区：

医学2区

文献类型：

作者：

Nishizawa，Masako;Yamamoto，Hiroyuki

目的：在HIV-1感染中，病毒特异性B细胞和中和抗体（NAb）反应受损，但对靶病毒包膜（Env）产生选择性压力，导致不同地理区域的序列差异显著。HIV Env特异性B细胞的基础诱导模式及其与HIV Env.Design的相互作用有待澄清：我们调查了Env多态性和Env特异性B细胞反应在治疗初治的HIV-1 CRF 01_AE感染的Vietnames.Methods：43例HIV-1 CRF 01_AE感染鉴定的个体的样本分为急性期（n= 12）和慢性期（n= 31）的血清学近期感染检测和临床参数的组合标准。我们量化了每个个体内血浆来源的Env可变区1-5（V1-V5）编码区中基于亚克隆的多态性残基位点数，将每个区域内的它们的总和指定为变异指数。检测外周血Env gp 140特异性B细胞反应和Env假病毒血浆中和活性，分析其与变异指数的关系。结果：检测HIV-1 CRF01_AE Env gp 140特异性总B细胞和浆细胞（CD 19 + IgD− CD 27 + CD 38 + CD 138+）反应。在慢性期样本中，所有Env V1-V5区域中的变异指数与Env特异性浆细胞应答显着相关，并且与总Env特异性B细胞应答相比，V1-V5总变异指数与Env特异性浆细胞的相关性更强。Env V5变异指数显着较高的慢性期交叉中和V5多态性/VRC 01不敏感的CRF01_AE Env。结论：结果显示之间的关联循环Env特异性浆细胞反应和Env多态性，暗示选择性压力Env浆细胞衍生的抗体，相反地表明，Env特异性B细胞诱导单独是不足以发挥Env选择性压力在HIV感染。

Objective:In HIV type 1 (HIV-1) infection, virus-specific B-cell and neutralizing antibody (NAb) responses are impaired but exert selective pressure on target viral Envelope (Env) resulting in prominent sequence diversification among geographical areas. The basal induction patterns of HIV Env-specific B cells and their interaction with HIV Env awaits clarification.Design:We investigated the relationship of Env polymorphisms and Env-specific B-cell responses in treatment-naive HIV-1 CRF01_AE-infected Vietnamese.Methods:Samples of 43 HIV-1 CRF01_AE infection-identified individuals were divided into acute-phase (n= 12) and chronic-phase (n= 31) by combined criteria of serological recent-infection assay and clinical parameters. We quantified subcloning-based polymorphic residue site numbers in plasma-derived Env variable region 1–5 (V1–V5)-coding regions within each individual, designating their summation within each region as variant index. Peripheral blood Env gp 140-specific B-cell responses and plasma neutralizing activity of Env pseudoviruses were examined to analyze their relationship with variant index.Results:HIV-1 CRF01_AE Env gp140-specific total B-cell and plasma cell (CD19+ IgD− CD27+ CD38+ CD138+) responses were determined. In chronic-phase samples, significant correlation of variant index in all Env V1–V5 regions with Env-specific plasma cell responses was shown, and V1–V5 total variant index correlated stronger with Env-specific plasma cell as compared with total Env-specific B-cell responses. Env V5 variant index was significantly higher in chronic-phase cross-neutralizers of V5-polymorphic/VRC01-insensitive CRF01_AE Env.Conclusion:Results revealed the association between circulating Env-specific plasma cell responses and Env polymorphisms, implicating selective pressure on Env by plasma cell-derived antibodies and conversely suggests that Env-specific B-cell induction alone is insufficient for exerting Env selective pressure in HIV infection.

Association of envelope-specific B-cell differentiation and viral selective pressure signatures in HIV-1 CRF01_AE infection

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