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高迁移率族蛋白盒1增强新感染原代T细胞中的HIV复制。

High Mobility Group Box 1 Protein Enhances HIV Replication in Newly Infected Primary T Cells.

作者信息

Trinh Quang D, Pham Ngan Thi Kim, Fuwa Kazumasa, Takada Kazuhide, Komine-Aizawa Shihoko, Honda Mitsuo, Ushijima Hiroshi, Hayakawa Satoshi

出版信息

Clin Lab. 2016 Dec 1;62(12):2305-2311. doi: 10.7754/Clin.Lab.2016.150928.

DOI:10.7754/Clin.Lab.2016.150928
PMID:28164548
Abstract

BACKGROUND

High-mobility group box 1 (HMGB1), a DNA-binding protein, has recently been shown to have effects on HIV replication, but the effects are dependent on the cell type and the timing of infection. Using human primary T cells, this study aimed to investigate the role of HMGB1 in HIV-1 replication in newly infected cells.

METHODS

Human primary T cells were infected with the HIV-1 LAI (X4) strain and then cultured in the presence of recombinant HMGB1 protein or an anti-HMGB1 antibody at various concentrations. At the indicated time points, HIV-1 p24 concentrations in the culture media were measured by ELISA. Cell proliferation, basal HMGB1 concentration, and CD3, CD4, CXCR4, and receptor for advanced glycation end products (RAGE) expression were also examined.

RESULTS

Recombinant HMGB1 could enhance HIV replication in newly infected primary T cells. In the presence of an anti-HMGB1 antibody (5 µg/mL or higher), significantly lower concentrations of HIV-1 p24 were observed in the cultures of primary T cells during the post-infection period.

CONCLUSIONS

The data presented suggest that HMGB1 plays a role in the enhancement of HIV-1 replication in newly infected T cells. This finding provides useful information toward understanding HIV pathogenesis and for the development of new therapeutic strategies.

摘要

背景

高迁移率族蛋白盒1(HMGB1)是一种DNA结合蛋白,最近研究表明其对HIV复制有影响,但这种影响取决于细胞类型和感染时间。本研究利用人原代T细胞,旨在探讨HMGB1在新感染细胞中对HIV-1复制的作用。

方法

用人原代T细胞感染HIV-1 LAI(X4)毒株,然后在不同浓度的重组HMGB1蛋白或抗HMGB1抗体存在的情况下进行培养。在指定时间点,通过酶联免疫吸附测定法检测培养基中HIV-1 p24的浓度。还检测了细胞增殖、基础HMGB1浓度以及CD3、CD4、CXCR4和晚期糖基化终产物受体(RAGE)的表达。

结果

重组HMGB1可增强新感染原代T细胞中的HIV复制。在存在抗HMGB1抗体(5μg/mL或更高)的情况下,在感染后时期原代T细胞培养物中观察到HIV-1 p24的浓度显著降低。

结论

所呈现的数据表明,HMGB1在增强新感染T细胞中HIV-1复制方面发挥作用。这一发现为理解HIV发病机制和开发新的治疗策略提供了有用信息。

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