HIV elite control is associated with reduced TRAILshort expression.
HIV elite control is associated with reduced TRAILshort expression.
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DOI：
10.1097/qad.0000000000002279
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发表时间：
2019-09
期刊：
影响因子：
3.8
通讯作者：
A. Paim;N. Cummins;S. Natesampillai;E. Garcia-Rivera;N. Kogan;U. Neogi;A. Sönnerborg;Maike Sperk;G. Bren;S. Deeks;E. Polley;A. Badley
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文献类型：
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作者：
A. Paim;N. Cummins;S. Natesampillai;E. Garcia-Rivera;N. Kogan;U. Neogi;A. Sönnerborg;Maike Sperk;G. Bren;S. Deeks;E. Polley;A. Badley
目的：tnf相关的凋亡诱导配体（TRAIL）依赖性凋亡与CD4 T细胞死亡和HIV-1感染的免疫控制有关。我们描述了一种称为TRAILshort的剪接变体，这是一种显性阴性配体，可在HIV-1感染的情况下拮抗trail诱导的细胞死亡。HIV-1的精英控制者自然地控制病毒复制，原因大部分未知。由于在TRAILshort低（或抑制）的情况下，感染细胞的死亡可能会加剧，因此我们测试了精英控制者状态与TRAILshort表达水平降低之间是否存在关联。DESIGN队列研究比较来自两个独立人群的HIV-1精英控制者和病毒进展者的TRAIL短链和全长TRAIL表达。方法采用RNAseq法检测PBMCs中TRAIL - short和TRAIL基因的表达。采用抗体头阵列法和接近延伸法分别检测血浆中TRAIL - short和TRAIL蛋白的表达。结果与病毒血症进展者相比，HIV-1 Elite控制者在PBMCs中表达较少的TRAILshort转录本（P = 0.002），血浆中表达较少的TRAILshort蛋白（P < 0.001）。结论：pbmc和血浆中trail - short表达减少与HIV-1精英控制者状态相关。
OBJECTIVE TNF-Related Apoptosis-Inducing Ligand (TRAIL) dependent apoptosis has been implicated in CD4 T cell death and immunologic control of HIV-1 infection. We have described a splice variant called TRAILshort, which is a dominant negative ligand that antagonizes TRAIL-induced cell death in the context of HIV-1 infection. HIV-1 elite controllers naturally control viral replication for largely unknown reasons. Since enhanced death of infected cells might be responsible, as might occur in situations of low (or inhibited) TRAILshort, we tested whether there was an association between elite controller status and reduced levels of TRAILshort expression. DESIGN Cohort study comparing TRAILshort and full length TRAIL expression between HIV-1 elite controllers and viremic progressors from two independent populations. METHODS TRAILshort and TRAIL gene expression in PBMCs was determined by RNAseq. TRAILshort and TRAIL protein expression in plasma was determined by antibody bead array and proximity extension assay respectively. RESULTS HIV-1 Elite controllers expressed less TRAILshort transcripts in PBMCs (P = 0.002) and less TRAILshort protein in plasma (P < 0.001) than viremic progressors. CONCLUSIONS Reduced TRAILshort expression in PBMCs and plasma is associated with HIV-1 elite controller status.