Effects of Tat proteins and Tat mutants of different human immunodeficiency virus type 1 clades on glial JC virus early and late gene transcription.
Effects of Tat proteins and Tat mutants of different human immunodeficiency virus type 1 clades on glial JC virus early and late gene transcription.
复制标题
1型人类免疫缺陷病毒不同进化枝的Tat蛋白和Tat突变体对胶质JC病毒早期和晚期基因转录的影响。
DOI：
10.1099/vir.0.047902-0
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发表时间：
2013
期刊：
影响因子：
--
通讯作者：
Johnson,EdwardM
中科院分区：
文献类型：
--
作者：
Wright,ClaytonA;Nance,JonasA;Johnson,EdwardM
JC多瘤病毒（JCV）是进行性多灶性白质脑病（PML）的病原体，PML是一种常见的致命性脑感染，在美国约有4%的艾滋病患者受到感染。 人类免疫缺陷病毒1型（HIV-1）达特与细胞蛋白在JCV非编码控制区（NCCR）共同作用，可刺激JCV DNA转录和复制。脑中的达特由HIV-1感染的细胞分泌，并由少突胶质细胞（能够被JCV感染的细胞）掺入。到目前为止，达特对JCV的影响主要是用北美最常见的HIV-1 B进化枝编码的蛋白质研究的。在这里，我们确定的能力，达特从不同的HIV-1分支改变JCV早期和晚期基因转录和DNA复制开始在JCV的起点。来自测试的所有进化枝的达特刺激JCV早期和晚期基因启动子，其中进化枝B达特显著最有效。来自HIV-1进化枝的达特蛋白在其对HIV-1和JCV转录的作用中显示出平行的差异模式，表明在这两种情况下达特作用由相同的细胞蛋白介导。分化体B达特在将肿瘤生长因子β和细胞伴侣Purα的Smad介导剂导向NCCR方面最有效。来自所有非B进化枝的达特蛋白抑制JCV DNA复制的起始。HIV-1进化枝B达特在促进JCV转录和复制过程中的有效性强调了需要进一步研究以确定来自不同HIV-1亚株的达特的哪些分子方面可以有助于neuroAIDS中PML发展的过程。
Polyomavirus JC (JCV) is the aetiological agent of progressive multifocal leukoencephalopathy (PML), a frequently fatal infection of the brain afflicting nearly 4 % of AIDS patients in the USA. Human immunodeficiency virus type 1 (HIV-1) Tat, acting together with cellular proteins at the JCV non-coding control region (NCCR), can stimulate JCV DNA transcription and replication. Tat in the brain is secreted by HIV-1-infected cells and incorporated by oligodendroglia, cells capable of infection by JCV. Thus far the effects of Tat on JCV have been studied primarily with protein encoded by the HIV-1 B clade most common in North America. Here, we determine the abilities of Tat from different HIV-1 clades to alter JCV early and late gene transcription and DNA replication initiated at the JCV origin. Tat from all clades tested stimulates both JCV early and late gene promoters, with clade B Tat being significantly most effective. Tat proteins from the HIV-1 clades display parallel patterns of differences in their effects on HIV-1 and JCV transcription, suggesting that Tat effects in both cases are mediated by the same cellular proteins. Clade B Tat is most effective at directing Smad mediators of tumour growth factor beta and cellular partner Purα to the NCCR. Tat proteins from all non-B clades inhibit initiation of JCV DNA replication. The effectiveness of HIV-1 clade B Tat at promoting JCV transcriptional and replicative processes highlights a need for further investigation to determine which molecular aspects of Tat from distinct HIV-1 substrains can contribute to the course of PML development in neuroAIDS.