Bone marrow stromal antigen 2 (BST-2) genetic variants influence expression levels and disease outcome in HIV-1 chronically infected patients.

IF 2.7 3区医学 Q3 VIROLOGY

Retrovirology Pub Date : 2022-01-26 DOI:10.1186/s12977-022-00588-2

Hlelolwenkosi Mlimi, Kewreshini K Naidoo, Jenniffer Mabuka, Thumbi Ndung'u, Paradise Madlala

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Abstract

Background: Bone marrow stromal antigen 2 (BST-2) also known as Tetherin (CD317/HM1.24), is a host restriction factor that blocks the release of HIV-1 virions from infected cells. Previous studies reported that BST-2 genetic variants or single nucleotide polymorphims (SNPs) have a preventative role during HIV-1 infection. However, the influence of BST-2 SNPs on expression levels remains unknown. In this study, we investigated the influence of BST-2 SNPs on expression levels and disease outcome in HIV-1 subtype C chronically infected antiretroviral therapy naïve individuals.

Results: We quantified BST-2 mRNA levels in peripheral blood mononuclear cells (PBMCs), determined BST-2 protein expression on the surface of CD4⁺ T cells using flow cytometry and genotyped two intronic single nucleotide polymorphisms (SNPs) rs919267 and rs919266 together with one SNP rs9576 located in the 3' untranslated region (UTR) of bst-2 gene using TaqMan assays from HIV-1 uninfected and infected participants. Subsequently, we determined the ability of plasma antibody levels to mediate antibody-dependent cellular phagocytosis (ADCP) using gp120 consensus C and p24 subtype B/C protein. Fc receptor-mediated NK cell degranulation was evaluated as a surrogate for ADCC activity using plasma from HIV-1 positive participants. BST-2 mRNA expression levels in PBMCs and protein levels on CD4⁺ T cells were lower in HIV-1 infected compared to uninfected participants (p = 0.075 and p < 0.001, respectively). rs919267CT (p = 0.042) and rs919267TT (p = 0.045) were associated with lower BST-2 mRNA expression levels compared to rs919267CC in HIV-1 uninfected participants. In HIV-1 infected participants, rs919267CT associated with lower CD4 counts, (p = 0.003), gp120-IgG1 (p = 0.040), gp120-IgG3 (p = 0.016) levels but higher viral loads (p = 0.001) while rs919267TT was associated with lower BST-2 mRNA levels (p = 0.046), CD4 counts (p = 0.001), gp120-IgG1 levels (p = 0.033) but higher plasma viral loads (p = 0.007). Conversely, rs9576CA was associated with higher BST-2 mRNA expression levels (p = 0.027), CD4 counts (p = 0.079), gp120-IgG1 (p = 0.009), gp120-IgG3 (p = 0.039) levels but with lower viral loads (p = 0.037).

Conclusion: Our findings show that bst-2 SNPs mediate BST-2 expression and disease outcome, correlate with gp120-IgG1, gp120-IgG3 levels but not p24-IgG levels, ADCC and ADCP activity.

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骨髓基质抗原2 (BST-2)基因变异影响HIV-1慢性感染患者的表达水平和疾病结局。

背景:骨髓基质抗原2 (BST-2)也被称为Tetherin (CD317/HM1.24)，是一种阻止HIV-1病毒粒子从感染细胞释放的宿主限制因子。先前的研究报道BST-2遗传变异或单核苷酸多态性(snp)在HIV-1感染中具有预防作用。然而，BST-2 snp对表达水平的影响尚不清楚。在这项研究中，我们研究了BST-2 snp对HIV-1亚型C慢性感染抗逆转录病毒治疗naïve个体的表达水平和疾病结局的影响。结果:我们量化了外周血单核细胞(PBMCs) BST-2 mRNA水平，流式细胞术检测了CD4+ T细胞表面BST-2蛋白的表达，并使用TaqMan方法对未感染和感染HIV-1的参与者进行了两个内含子单核苷酸多态性(SNP) rs919267和rs919266以及位于BST-2基因3'非翻译区(UTR)的一个SNP rs9576进行了基因分型。随后，我们利用gp120共识C和p24亚型B/C蛋白确定了血浆抗体水平介导抗体依赖性细胞吞噬(ADCP)的能力。使用HIV-1阳性参与者的血浆评估Fc受体介导的NK细胞脱颗粒作为ADCC活性的替代品。HIV-1感染者外周血中BST-2 mRNA表达水平和CD4+ T细胞蛋白水平均低于未感染者(p = 0.075和p)。结论:BST-2 snp介导BST-2表达和疾病预后，与gp120-IgG1、gp120-IgG3水平相关，但与p24-IgG水平、ADCC和ADCP活性无关。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Retrovirology 医学-病毒学

CiteScore

5.80

自引率

3.00%

发文量

审稿时长

>0 weeks

期刊介绍： Retrovirology is an open access, online journal that publishes stringently peer-reviewed, high-impact articles on host-pathogen interactions, fundamental mechanisms of replication, immune defenses, animal models, and clinical science relating to retroviruses. Retroviruses are pleiotropically found in animals. Well-described examples include avian, murine and primate retroviruses. Two human retroviruses are especially important pathogens. These are the human immunodeficiency virus, HIV, and the human T-cell leukemia virus, HTLV. HIV causes AIDS while HTLV-1 is the etiological agent for adult T-cell leukemia and HTLV-1-associated myelopathy/tropical spastic paraparesis. Retrovirology aims to cover comprehensively all aspects of human and animal retrovirus research.