Differential Regulation of HIV-1 Clade-Specific B, C, and E Long Terminal Repeats by NF-κB and the Tat Transactivator

IF 2.8 3区 医学 Q3 VIROLOGY Virology Pub Date : 2002-04-25 DOI:10.1006/viro.2001.1397
Philippe Roof , Maria Ricci , Pierre Genin , Monty A. Montano , Max Essex , Mark A. Wainberg , Anne Gatignol , John Hiscott
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Abstract

The major group of human immunodeficiency viruses (HIV-1) that comprise the current global pandemic have diversified during their worldwide spread and may be divided into at least 10 distinct subtypes or clades, A through J. Subtype B predominates in North America and Europe, subtype E predominates in Southeast Asia, and subtype C predominates in sub-Saharan Africa. Functional distinctions in long terminal repeat (LTR) architecture among HIV subtypes have been identified, thus raising the possibility that regulatory divergence among the subtypes of HIV-1 has occurred. In addition to the transcriptional specificity of the HIV-1 LTR, productive HIV-1 replication is also dependent upon the viral Tat protein. Therefore, we sought to investigate whether interactions between host signaling pathways and the NF-κB regions of different HIV-1 subtypes, together with subtype-specific interactions between Tat, TAR, and cellular proteins, modulate the efficiency of HIV-1 clade-specific gene transcription. We demonstrate that the NF-κB sites of subtypes B and E both bind NF-κB-related complexes. However, the duplicated κB sites of the C subtype do not compete for NF-κB binding. Also, clade E Tat protein possesses the highest transactivation capacity, regardless of the LTR context. Furthermore, preliminary evidence suggests that the acetylation of subtype-specific Tat proteins may correlate with their transactivation efficiency.
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NF-kappaB和Tat反激活子对HIV-1进化枝特异性B、C和E长末端重复序列的差异调控
构成当前全球流行病的人类免疫缺陷病毒(HIV-1)的主要群体在其全球传播过程中已经多样化,并且可以分为至少10个不同的亚型或分支,A到j。B亚型在北美和欧洲占主导地位,E亚型在东南亚占主导地位,C亚型在撒哈拉以南非洲占主导地位。HIV亚型之间长末端重复序列(LTR)结构的功能差异已经被确定,从而提高了HIV-1亚型之间发生调控差异的可能性。除了HIV-1 LTR的转录特异性外,多产的HIV-1复制也依赖于病毒Tat蛋白。因此,我们试图研究宿主信号通路与不同HIV-1亚型的NF-kappaB区域之间的相互作用,以及Tat、TAR和细胞蛋白之间的亚型特异性相互作用是否调节HIV-1进化枝特异性基因转录的效率。我们证明,亚型B和E的NF-kappaB位点都结合NF-kappaB相关复合物。然而,C亚型的重复kappaB位点不竞争NF-kappaB结合。此外,无论LTR背景如何,进化枝E Tat蛋白都具有最高的交互激活能力。此外,初步证据表明,亚型特异性Tat蛋白的乙酰化可能与其交易激活效率相关。
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来源期刊
Virology
Virology 医学-病毒学
CiteScore
6.00
自引率
0.00%
发文量
157
审稿时长
50 days
期刊介绍: Launched in 1955, Virology is a broad and inclusive journal that welcomes submissions on all aspects of virology including plant, animal, microbial and human viruses. The journal publishes basic research as well as pre-clinical and clinical studies of vaccines, anti-viral drugs and their development, anti-viral therapies, and computational studies of virus infections. Any submission that is of broad interest to the community of virologists/vaccinologists and reporting scientifically accurate and valuable research will be considered for publication, including negative findings and multidisciplinary work.Virology is open to reviews, research manuscripts, short communication, registered reports as well as follow-up manuscripts.
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