期刊
JOURNAL OF VIROLOGY
卷 82, 期 4, 页码 1870-1883出版社
AMER SOC MICROBIOLOGY
DOI: 10.1128/JVI.02228-07
关键词
-
类别
资金
- NIAID NIH HHS [R01 AI051178, AI43222, R01 AI043222, R37 AI051178, AI51178] Funding Source: Medline
The mechanism of CD4(+) T-cell depletion during chronic human immunodeficiency virus type 1 (HIV-1) infection remains unknown. Many studies suggest a significant role for chronic CD4(+) T-cell activation. We assumed that the pathogenic process of excessive CD4(+) T-cell activation would be reflected in the transcriptional profiles of activated CD4(+) T cells. Here we demonstrate that the transcriptional programs of in vivo-activated CD4(+) T cells from untreated HIV-positive (HIV+) individuals are clearly different from those of activated CD4(+) T cells from HIV-negative (HIV-) individuals. We observed a dramatic up-regulation of cell cycle-associated and interferon-stimulated transcripts in activated CD4(+) T cells of untreated HIV+ individuals. Furthermore, we find an enrichment of proliferative and type I interferon-responsive transcription factor binding sites in the promoters of genes that are differentially expressed in activated CD4(+) T cells of untreated HIV+ individuals compared to those of HIV- individuals. We confirm these findings by examination of in vivo-activated CD4(+) T cells. Taken together, these results suggest that activated CD4(+) T cells from untreated HIV+ individuals are in a hyperproliferative state that is modulated by type I interferons. From these results, we propose a new model for CD4(+) T-cell depletion during chronic HIV-1 infection.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据