Proteome and Protein Network Analyses of Memory T Cells Find Altered Translation and Cell Stress Signaling in Treated Human Immunodeficiency Virus Patients Exhibiting Poor CD4 Recovery.
Proteome and Protein Network Analyses of Memory T Cells Find Altered Translation and Cell Stress Signaling in Treated Human Immunodeficiency Virus Patients Exhibiting Poor CD4 Recovery.
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DOI：
10.1093/ofid/ofw037
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发表时间：
2016-03
影响因子：
4.2
通讯作者：
Sieg SF
中科院分区：
文献类型：
--
作者：
Azzam S;Schlatzer D;Maxwell S;Li X;Bazdar D;Chen Y;Asaad R;Barnholtz-Sloan J;Chance MR;Sieg SF
背景：人类免疫缺陷病毒（HIV）患者在抗逆转录病毒治疗（ART）期间，尽管病毒得到抑制，但CD4 T细胞恢复较差，被称为免疫无应答者。 ART期间不完全免疫恢复的分子机制尚未完全了解。方法：采用单细胞型中央记忆T细胞的无标记定量蛋白质组学方法，揭示无应答者、应答者（ART期间CD4恢复良好）和健康个体之间的相对蛋白质丰度变化。 蛋白质组的变化进行了蛋白质通路和网络分析，并验证了选择性反应监测质谱。结果：各组蛋白质组学分析从1500个非冗余蛋白质中检测到155个重要蛋白质。 通路和网络分析显示，与应答者和对照组相比，无应答者受试者的雷帕霉素和蛋白抑制相关蛋白的哺乳动物靶点失调，应激反应相关蛋白减少。对于HIV应答者和无应答者，肌动蛋白细胞骨架信号传导均增加。结论：与应答者和对照组相比，来自免疫无应答者的记忆T细胞中与运动和蛋白翻译相关的蛋白质增加，而能够对细胞应激做出反应的蛋白质减少。 T细胞管理压力和调节代谢的潜力可能有助于它们重建淋巴细胞减少宿主的能力。
Background. Human immunodeficiency virus (HIV) patients who experience poor CD4 T-cell recovery despite viral suppression during antiretroviral therapy (ART) are known as immunological nonresponders. The molecular mechanism(s) underlying incomplete immune restoration during ART is not fully understood. Methods. Label-free quantitative proteomics on single-cell type central memory T cells were used to reveal relative protein abundance changes between nonresponder, responder (good CD4 recovery during ART), and healthy individuals. Proteome changes were analyzed by protein pathway and network analyses and verified by selected reaction monitoring mass spectrometry. Results. Proteomic analysis across groups detected 155 significant proteins from 1500 nonredundant proteins. Pathway and network analyses revealed dysregulation in mammalian target of rapamycin and protein translation-related proteins and decreases in stress response-related proteins for nonresponder subjects compared with responders and controls. Actin cytoskeleton signaling was increased for HIV responders and nonresponders alike. Conclusions. Memory T cells from immunologic nonresponders have increases in proteins related to motility and protein translation and decreases in proteins capable of responding to cellular stresses compared with responders and controls. The potential for T cells to manage stress and modulate metabolism may contribute to their capacity to reconstitute a lymphopenic host.