Transcriptomics and Targeted Proteomics Analysis to Gain Insights Into the Immune-control Mechanisms of HIV-1 Infected Elite Controllers

被引:24
|
作者
Zhang, Wang [1 ,2 ]
Ambikan, Anoop T. [1 ]
Sperk, Maike [1 ,3 ]
van Domselaar, Robert [4 ]
Nowak, Piotr [1 ,4 ]
Noyan, Kajsa [1 ]
Russom, Aman [2 ]
Sonnerborg, Anders [1 ,4 ]
Neogi, Ujjwal [1 ,2 ]
机构
[1] Karolinska Inst, Dept Lab Med, Div Clin Microbiol, F68, S-14186 Stockholm, Sweden
[2] KTH Royal Inst Technol, Div Prote & Nanobiotechnol, Sci Life Lab, Stockholm, Sweden
[3] Univ Tubingen, Fac Med, Tubingen, Germany
[4] Karolinska Inst, Karolinska Univ Hosp, Infect Dis Unit, Dept Med Huddinge, Stockholm, Sweden
来源
EBIOMEDICINE | 2018年 / 27卷
基金
瑞典研究理事会;
关键词
HIV-1 Elite Controllers; Transcriptome; Proteome; HLA CLASS-I; NEGATIVE REGULATORS; HIV; EXPRESSION; INFECTION; PROTEIN; CELLS; ACTIVATION; CC;
D O I
10.1016/j.ebiom.2017.11.031
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
A small subset of HIV-1 infected individuals, the "Elite Controllers" (EC), can control viral replication and restrain progression to immunodeficiency without antiretroviral therapy (ART). In this study, a cross-sectional transcriptomics and targeted proteomics analysis were performed in a well-defined Swedish cohort of untreated EC (n = 19), treatment naive patients with viremia (VP, n = 32) and HIV-1-negative healthy controls (HC, n = 23). The blood transcriptome identified 151 protein-coding genes that were differentially expressed (DE) in VP compared to EC. Genes like CXCR6 and SIGLEC1were downregulated in EC compared to VP. A definite distinction in gene expression between males and females among all patient-groups were observed. The gene expression profile between female EC and the healthy females was similar but did differ between male EC and healthy males. At targeted proteomics analysis, 90% (29/32) of VPs clustered together while EC and HC clustered separately from VP. Among the soluble factors, 33 were distinctive to be statistically significant (False discovery rate = 0.02). Cell surface receptor signaling pathway, programmed cell death, response to cytokine and cytokine-mediated signaling seem to synergistically play an essential role in HIV-1 control in EC. (c) 2017 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license.
引用
收藏
页码:40 / 50
页数:11
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