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1型人类免疫缺陷病毒(HIV-1)在肠道上皮细胞中的感染与表达:蛋白激酶A和C通路在HIV-1转录中的作用

Human immunodeficiency virus type 1 (HIV-1) infection and expression in intestinal epithelial cells: role of protein kinase A and C pathways in HIV-1 transcription.

作者信息

Kagnoff M F, Roebuck K A

机构信息

Department of Medicine, University of California, San Diego, La Jolla, CA 92093-0623, USA.

出版信息

J Infect Dis. 1999 May;179 Suppl 3:S444-7. doi: 10.1086/314801.

DOI:10.1086/314801
PMID:10099116
Abstract

Human immunodeficiency virus (HIV) can infect human colon epithelial cell lines by both CD4-dependent and -independent mechanisms. The present studies assessed cellular factors that are important for HIV-1 transcription in human colon epithelial cells. The HIV-1 long terminal repeat (LTR) was shown to contain functional DNA cis-regulatory elements downstream of the viral transactivator-responsive element in the transcribed noncoding 5' leader sequence. These downstream regulatory elements, termed DSE, can bind c-Fos and JunD and transmit protein kinase C activation signals to the HIV LTR. Moreover, specific Jun and Fos transcription factors can transactivate HIV-1 provirus in human colon epithelial cells. The DSE also bind related proteins of the CREB/ATF family. In this regard, the DSE behave as 12-0-tetradecanoylphorbol 13-acetate responder element-like cAMP-responsive elements because they bind both AP-1 and CREB/ATF transcription factors, thereby permitting induction of the HIV-1 LTR by both protein kinase C and A activation signals.

摘要

人类免疫缺陷病毒(HIV)可通过依赖CD4和不依赖CD4的机制感染人结肠上皮细胞系。本研究评估了对人结肠上皮细胞中HIV-1转录至关重要的细胞因子。研究表明,HIV-1长末端重复序列(LTR)在转录的非编码5'前导序列中,病毒反式激活因子应答元件下游含有功能性DNA顺式调控元件。这些下游调控元件称为DSE,可结合c-Fos和JunD,并将蛋白激酶C激活信号传递至HIV LTR。此外,特定的Jun和Fos转录因子可在人结肠上皮细胞中转录激活HIV-1前病毒。DSE还可结合CREB/ATF家族的相关蛋白。就此而言,DSE表现为12-0-十四烷酰佛波醇-13-乙酸酯反应元件样的环磷酸腺苷反应元件,因为它们可结合AP-1和CREB/ATF转录因子,从而允许通过蛋白激酶C和A激活信号诱导HIV-1 LTR。

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