Proliferative activity of extracellular HIV-1 Tat protein in human epithelial cells: expression profile of pathogenetically relevant genes.
Proliferative activity of extracellular HIV-1 Tat protein in human epithelial cells: expression profile of pathogenetically relevant genes.
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DOI：
10.1186/1471-2180-5-20
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发表时间：
2005-04-27
期刊：
影响因子：
4.2
通讯作者：
Toniolo AQ
中科院分区：
文献类型：
--
作者：
Bettaccini AA;Baj A;Accolla RS;Basolo F;Toniolo AQ
达特正在作为艾滋病毒疫苗的一种成分进行测试。达特活性主要在淋巴/造血谱系细胞上进行研究。然而，已知HIV-1感染实体器官和粘膜表面的许多不同细胞。在低血清条件下培养的乳腺和羊膜上皮细胞上研究了双外显子（aa 1-101）和合成（aa 1-86）达特的活性。小浓度的达特（100 ng/ml）刺激细胞增殖。达特抗体中和了促有丝分裂的达特活性。RT-PCR和基因芯片技术检测Tat处理后细胞基因表达的变化。在处理的4小时内，暴露于达特之后，一些细胞周期相关基因上调（转录因子、细胞周期蛋白/cdk复合物、凋亡途径的基因）和与HIV发病机制相关的基因[趋化因子受体（CXCR 4，CCR 3），趋化细胞因子（SDF-1、RANTES、SCYC 1、SCYE 1）、IL 6家族细胞因子、炎性细胞因子、TGF-β家族因子（TGF β、BMP-1、BMP-2）]。抗炎性细胞因子（IL-10、IL-19、IL-20）的上调是其他持续性病毒感染的标志，是Tat处理的上皮细胞系的显著特征。细胞外达特对乳腺和羊膜上皮细胞是促有丝分裂的，并刺激HIV感染中致病相关基因的表达。这些作用可能有利于病毒复制，并可能促进病毒的母婴传播。
Tat is being tested as a component of HIV vaccines. Tat activity has been mainly investigated on cells of lymphoid/hematopoietic lineages. HIV-1, however, is known to infect many different cells of both solid organs and mucosal surfaces. The activity of two-exon (aa 1–101) and synthetic (aa 1–86) Tat was studied on mammary and amniotic epithelial cells cultured under low serum conditions. small concentrations of Tat (100 ng/ml) stimulated cell proliferation. Tat antibodies neutralized the mitogenic Tat activity. Changes of gene expression in Tat-treated cells were evaluated by RT-PCR and gene-array methods. Within 4 hours of treatment, exposure to Tat is followed by up-regulation of some cell cycle-associated genes (transcription factors, cyclin/cdk complexes, genes of apoptotic pathways) and of genes relevant to HIV pathogenesis [chemokine receptors (CXCR4, CCR3), chemotactic cytokines (SDF-1, RANTES, SCYC1, SCYE1), IL6 family cytokines, inflammatory cytokines, factors of the TGF-beta family (TGFb, BMP-1, BMP-2)]. Up-regulation of anti-inflammatory cytokines (IL-10, IL-19, IL-20), a hallmark of other persistent viral infections, was a remarkable feature of Tat-treated epithelial cell lines. extracellular Tat is mitogenic for mammary and amniotic epithelial cells and stimulates the expression of genes of pathogenetic interest in HIV infection. These effects may favor virus replication and may facilitate the mother-to-child transmission of virus.
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