Distinct transcriptional profiles in ex vivo CD4+ and CD8+ T cells are established early in human immunodeficiency virus type 1 infection and are characterized by a chronic interferon response as well as extensive transcriptional changes in CD8+ T cells
Distinct transcriptional profiles in ex vivo CD4+ and CD8+ T cells are established early in human immunodeficiency virus type 1 infection and are characterized by a chronic interferon response as well as extensive transcriptional changes in CD8+ T cells
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DOI：
10.1128/jvi.01552-06
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发表时间：
2007-04-01
影响因子：
5.4
通讯作者：
Der, Sandy D.
中科院分区：
文献类型：
--
作者：
Hyrcza, Martin D.;Kovacs, Colin;Der, Sandy D.
T细胞功能的变化是人类免疫缺陷病毒1型（HIV-1）感染的标志，但导致这些变化的致病机制尚不清楚。我们检测了来自未治疗的HIV-1感染者在不同临床阶段和疾病进展速度的离体人CD4（+）和CD8（+）T细胞中的基因表达谱。来自病毒血症得到控制的HIV-1感染非进展者的纯CD 4（+）和CD 8（+）T细胞亚群的特征与未感染HIV-1的个体的特征难以区分。同样，没有基因簇可以区分早期感染者的T细胞与慢性进行性HIV-1感染者的T细胞，而未感染者或非进展者与早期或慢性进展者之间观察到差异。在早期和慢性HIV-1感染中，观察到三种特征性基因表达特征。(i)CD4（+）和CD8（+）T细胞显示干扰素刺激基因（ISG）表达增加。然而，一些ISG，包括CXCL9，CXCL10和CXCL11，以及白细胞介素-15 α受体没有上调。(ii)CD4（+）和CD8（+）T细胞显示与胸腺细胞中观察到的相似的簇。(iii)与CD4（+）T细胞相比，更多的基因在CD8（+）T细胞中差异调节，包括一组仅在CD8（+）T细胞中下调的基因。总之，HIV-1感染诱导持久的T细胞转录谱，在感染早期，其特征在于一个戏剧性的，但可能异常的干扰素反应和一个配置文件表明一个积极的胸腺输出。这些发现突出了HIV-1感染中宿主-病毒关系的复杂性。
Changes in T-cell function are a hallmark of human immunodeficiency virus type 1 (HIV-1) infection, but the pathogenic mechanisms leading to these changes are unclear. We examined the gene expression profiles in ex vivo human CD4(+) and CD8(+) T cells from untreated HIV-1-infected individuals at different clinical stages and rates of disease progression. Profiles of pure CD4(+) and CD8(+) T-cell subsets from HIV-1-infected nonprogressors with controlled viremia were indistinguishable from those of individuals not infected with HIV-1. Similarly, no gene clusters could distinguish T cells from individuals with early infection from those seen in chronic progressive HIV-1 infection, whereas differences were observed between uninfected individuals or nonprogressors versus early or chronic progressors. In early and chronic HIV-1 infection, three characteristic gene expression signatures were observed. (i) CD4(+) and CD8(+) T cells showed increased expression of interferon-stimulated genes (ISGs). However, some ISGs, including CXCL9, CXCL10, and CXCL11, and the interieukin-15 alpha receptor were not upregulated. (ii) CD4(+) and CD8(+) T cells showed a cluster similar to that observed in thymocytes. (iii) More genes were differentially regulated in CD8(+) T cells than in CD4(+) T cells, including a cluster of genes downregulated exclusively in CD8(+) T cells. In conclusion, HIV-1 infection induces a persistent T-cell transcriptional profile, early in infection, characterized by a dramatic but potentially aberrant interferon response and a profile suggesting an active thymic output. These findings highlight the complexity of the host-virus relationship in HIV-1 infection.