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利用 OMICs 方法发现候选 HIV-1 潜伏期生物标志物。

Discovery of candidate HIV-1 latency biomarkers using an OMICs approach.

机构信息

Department of Medical Microbiology and Immunology, Creighton University, Omaha, NE, USA.

Department of Medical Microbiology and Immunology, Creighton University, Omaha, NE, USA.

出版信息

Virology. 2021 Jun;558:86-95. doi: 10.1016/j.virol.2021.03.003. Epub 2021 Mar 11.

Abstract

Infection with HIV-1 remains uncurable due to reservoirs of latently infected cells. Any potential cure for HIV will require a mechanism to identify and target these cells in vivo. We created a panel of Jurkat cell lines latently infected with the HIV DuoFlo virus to identify candidate biomarkers of latency. SWATH mass spectrometry was used to compare the membrane proteomes of one of the cell lines to parental Jurkat cells. Several candidate proteins with significantly altered expression were identified. The differential expression of several candidates was validated in multiple latently infected cell lines. Three factors (LAG-3, CD147,CD231) were altered across numerous cell lines, but the expression of most candidate biomarkers was variable. These results confirm that phenotypic differences in latently infected cells exists and identify additional novel biomarkers. The variable expression of biomarkers across different cell clones suggests universal antigen-based detection of latently infected cells may require a multiplex approach.

摘要

由于潜伏感染细胞的存在,HIV-1 的感染仍然无法治愈。任何潜在的 HIV 治疗方法都需要一种机制来在体内识别和靶向这些细胞。我们创建了一组潜伏感染 HIV DuoFlo 病毒的 Jurkat 细胞系,以鉴定潜伏的候选生物标志物。SWATH 质谱法用于比较其中一个细胞系与亲本 Jurkat 细胞的膜蛋白质组。鉴定出几种表达明显改变的候选蛋白。在多个潜伏感染细胞系中验证了几个候选物的差异表达。三种因子(LAG-3、CD147、CD231)在多个细胞系中发生改变,但大多数候选生物标志物的表达是可变的。这些结果证实了潜伏感染细胞中存在表型差异,并确定了其他新的生物标志物。不同细胞克隆中生物标志物的可变表达表明,基于普遍抗原的潜伏感染细胞检测可能需要采用多重方法。

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