Differential transcriptional regulation by human immunodeficiency virus type 1 and gp120 in human astrocytes

Differential transcriptional regulation by human immunodeficiency virus type 1 and gp120 in human astrocytes
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DOI:
10.1080/13550280390201119
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发表时间:
2003-06-01
影响因子:
3.2
通讯作者:
Nath, A
Nath, A
中科院分区:
医学4区
文献类型:
--
作者:
Galey, D;Becker, K;Nath, A

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星形胶质细胞可能感染人类免疫缺陷病毒1型(HIV-1)或暴露于HIV蛋白gp 120,但它们在HIV痴呆发病机制中的作用在很大程度上是未知的。为了表征HIV对星形胶质细胞转录的影响,进行了微阵列分析和核糖核酸酶保护测定(RPA)。星形胶质细胞感染HIV或gp 120治疗对基因转录有差异和深远的影响。在基于免疫的阵列上的1153个寡核苷酸中,108个基因(53个上升; 55个下降)和82个基因(32个上升; 50个下降)的表达分别受到gp 120和HIV感染的显著调节。在基于神经的阵列上的1153个寡核苷酸中,58个基因(25个向上; 33个向下)和47个基因(17个向上; 30个向下)分别被gp 120和HIV感染显著调节。趋化因子和细胞因子的诱导主要发生在HIV感染,而gp 120没有显着的影响。RPA证实了这些结果。作者得出结论,星形胶质细胞功能的深刻改变发生在对HIV感染或与病毒蛋白相互作用的反应中,表明星形胶质细胞可能在HIV痴呆的发病机制中发挥重要作用。
Astrocytes may be infected with the human immunodeficiency virus type 1 (HIV-1) or exposed to the HIV protein gp120, yet their role in the pathogenesis of HIV dementia is largely unknown. To characterize the effects of HIV on astrocytic transcription, microarray analysis and ribonuclease protection assays (RPA) were performed. Infection of astrocytes by HIV or treatment with gp120 had differential and profound effects on gene transcription. Of the 1153 oligonucleotides on the immune-based array, the expression of 108 genes (53 up; 55 down) and 82 genes (32 up; 50 down) were significantly modulated by gp120 and HIV infection respectively. Of the 1153 oligonucleotides on the neuro-based array, 58 genes (25 up; 33 down) and 47 genes (17 up; 30 down) were significantly modulated by gp120 and HIV infection respectively. Chemokine and cytokine induction occurred predominantly by HIV infection, whereas gp120 had no significant effect. These results were confirmed by RPA. The authors conclude that profound alterations of astrocytic function occur in response to HIV infection or interaction with viral proteins, suggesting that astrocytes may play an important role in the pathogenesis of HIV dementia.