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对接受抗逆转录病毒治疗的 HIV 感染患者血浆中蛋白质组变化的分析。

Profiling of proteome changes in plasma of HIV-infected patients receiving antiretroviral therapy.

机构信息

School of Life Sciences, Tsinghua University, Beijing, China.

Department of Obstetric & Gynecology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China.

出版信息

Proteomics Clin Appl. 2022 Nov;16(6):e2100099. doi: 10.1002/prca.202100099. Epub 2022 Oct 10.

Abstract

PURPOSE

Antiretroviral therapy (ART) prevents human immunodeficiency virus (HIV)-1 onward transmission and disease progression, leading to excellent prognosis in people living with HIV-1 (PWH). However, side effects, complications, and impaired immune reconstitution persist in some patients treated with ART. We aimed to profile proteome changes in plasma before and after ART to identify the molecular pathways altered by ART.

EXPERIMENTAL DESIGN

Quantitative proteomics analysis based on tandem mass tag (TMT) labeling was used to profile proteome changes of paired plasma samples from HIV-1 patients before receiving ART and after ART treatment.

RESULTS

A total of 1398 protein groups (PGs) were identified, in which 18 proteins were downregulated and 50 were upregulated in plasma from ART treated patients. Based on Ingenuity Pathway analysis (IPA), gap junction signaling and actin cytoskeleton signaling were enriched among upregulated proteins, while downregulated proteins were mainly participated in IL-15 signaling pathway. Patients with the low level of CSF1R and the high levels of MINPP1 and TGM3 showed better CD4 T-cell recovery.

CONCLUSIONS

The present study provided plasma proteome changes after ART to elucidate the underlying mechanistic pathways in response to ART, and also identified potential targets to prompt immune reconstitution.

摘要

目的

抗逆转录病毒疗法(ART)可预防人类免疫缺陷病毒(HIV-1)的传播和疾病进展,从而使 HIV-1 感染者(PWH)获得极佳的预后。然而,一些接受 ART 治疗的患者仍存在副作用、并发症和免疫重建受损等问题。我们旨在分析 ART 前后血浆中的蛋白质组变化,以确定 ART 改变的分子途径。

实验设计

采用基于串联质量标签(TMT)标记的定量蛋白质组学分析方法,对接受 ART 治疗前和治疗后的 HIV-1 患者配对血浆样本中的蛋白质组变化进行分析。

结果

共鉴定出 1398 个蛋白质组(PGs),其中 18 个蛋白在接受 ART 治疗的患者血浆中下调,50 个蛋白上调。基于 IPA 分析,上调蛋白主要富集于间隙连接信号和肌动蛋白细胞骨架信号,而下调蛋白主要参与 IL-15 信号通路。CSF1R 水平低、MINPP1 和 TGM3 水平高的患者 CD4+T 细胞恢复更好。

结论

本研究提供了 ART 后血浆蛋白质组的变化情况,以阐明对 ART 反应的潜在机制途径,并鉴定了促进免疫重建的潜在靶点。

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