Modifications in host cell cytoskeleton structure and function mediated by intracellular HIV-1 Tat protein are greatly dependent on the second coding exon.
Modifications in host cell cytoskeleton structure and function mediated by intracellular HIV-1 Tat protein are greatly dependent on the second coding exon.
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DOI：
10.1093/nar/gkq037
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发表时间：
2010-06
影响因子：
14.9
通讯作者：
Coiras M
中科院分区：
文献类型：
--
作者：
López-Huertas MR;Callejas S;Abia D;Mateos E;Dopazo A;Alcamí J;Coiras M
人类免疫缺陷病毒1型（HIV-1）调节因子Tat对病毒复制至关重要，因为它可以实现病毒转录物的完全延伸。它可以被释放到细胞外空间，被邻近细胞吸收，产生深刻的细胞骨架重排，导致细胞凋亡。相反，细胞内Tat被描述为防止细胞凋亡的保护器。该基因由两个编码外显子组成，产生101个氨基酸（aa）的蛋白质。第一个外显子（1-72aa）足以进行病毒转录延伸，第二个外显子（73-101 aa）似乎有助于非转录功能。我们观察到，在细胞内稳定表达Tat101的Jurkat细胞比表达Tat72的细胞表现出4倍的基因表达失调。我们进行了功能实验来评估这种放松管制的效果。首先，NF-κ b -、NF- at-和sp1依赖性转录活性在Jurkat-Tat101中显著增强，而Tat72诱导的激活程度较轻但有效。其次，细胞骨架相关功能，如细胞形态、增殖、趋化性、极化和肌动蛋白聚合在Jurkat-Tat101中发生了深刻的改变，而在Jurkat-Tat72中没有。最后，几个细胞表面受体的表达被细胞内Tat101而不是Tat72显著地破坏。因此，这些修饰很大程度上依赖于第二个外显子，它们可能与在hiv -1感染的T细胞中观察到的能量有关。
The human immunodeficiency virus type 1 (HIV-1) regulator Tat is essential for viral replication because it achieves complete elongation of viral transcripts. Tat can be released to the extracellular space and taken up by adjacent cells, exerting profound cytoskeleton rearrangements that lead to apoptosis. In contrast, intracellular Tat has been described as protector from apoptosis. Tat gene is composed by two coding exons that yield a protein of 101 amino acids (aa). First exon (1–72aa) is sufficient for viral transcript elongation and second exon (73–101 aa) appears to contribute to non-transcriptional functions. We observed that Jurkat cells stably expressing intracellular Tat101 showed gene expression deregulation 4-fold higher than cells expressing Tat72. Functional experiments were performed to evaluate the effect of this deregulation. First, NF-κB-, NF-AT- and Sp1-dependent transcriptional activities were greatly enhanced in Jurkat-Tat101, whereas Tat72 induced milder but efficient activation. Second, cytoskeleton-related functions as cell morphology, proliferation, chemotaxis, polarization and actin polymerization were deeply altered in Jurkat-Tat101, but not in Jurkat-Tat72. Finally, expression of several cell surface receptors was dramatically impaired by intracellular Tat101 but not by Tat72. Consequently, these modifications were greatly dependent on Tat second exon and they could be related to the anergy observed in HIV-1-infected T cells.
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影响因子：
14.9
作者：
Benson DA;Cavanaugh M;Clark K;Karsch-Mizrachi I;Lipman DJ;Ostell J;Sayers EW
通讯作者：
Sayers EW
影响因子：
11.4
作者：
ALCAMI, J;DELERA, TL;ARENZANASEISDEDOS, F
通讯作者：
ARENZANASEISDEDOS, F
影响因子：
64.8
作者：
BACHELERIE, F;ALCAMI, J;VIRELIZIER, JL
通讯作者：
VIRELIZIER, JL
DOI：
10.1073/pnas.152313899
发表时间：
2002-07-23
影响因子：
11.1
作者：
Agwale, SM;Shata, MT;Hone, DM
通讯作者：
Hone, DM
影响因子：
11.4
作者：
Baumli, Sonja;Lolli, Graziano;Johnson, Louise N.
通讯作者：
Johnson, Louise N.