Stability of HIV-1 subtype B and C Tat is associated with variation in the carboxyl-terminal region

Stability of HIV-1 subtype B and C Tat is associated with variation in the carboxyl-terminal region
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HIV-1 B 和 C 亚型 Tat 的稳定性与羧基末端区域的变异相关

DOI:
10.1007/s12250-016-3681-0
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发表时间:
2016-03
期刊:
影响因子:
5.5
通讯作者:
Kong Xiaohong
Kong Xiaohong
中科院分区:
医学2区
文献类型:
--
作者:
Zhao Xuechao;Qian Lingyu;Zhou Deyu;Qi Di;Liu Chang;Kong Xiaohong

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多功能反式激活蛋白TAT是HIV-1复制的重要调控蛋白,具有高度的序列多样性。许多实验研究都检测了HIV-1 B亚型中的TAT,但尽管全世界C亚型感染的发病率很高,但对C亚型TAT的研究还很缺乏。我们假设氨基酸的差异导致了TAT蛋白之间的功能差异。在本研究中,我们发现B亚型NL4-3TAT和C亚型分离株HIV1084I TAT通过过表达TAT-FLAG融合蛋白而表现出不同的稳定性。此外,1084I TAT比NL4-3TAT能更有效地激活LtR和NF-κB。在分析截短形式的TAT的活性时,我们发现TAT的羧基末端区域调节其稳定性和反式活性。根据我们的结果,我们推测B-TAT和C-TAT在稳定性上的差异导致了反式激活能力的不同。
The multifunctional trans-activator Tat is an essential regulatory protein for HIV-1 replication and is characterized by high sequence diversity. Numerous experimental studies have examined Tat in HIV-1 subtype B, but research on subtype C Tat is lacking, despite the high prevalence of infections caused by subtype C worldwide. We hypothesized that amino acid differences contribute to functional differences among Tat proteins. In the present study, we found that subtype B NL4-3 Tat and subtype C isolate HIV1084i Tat exhibited differences in stability by overexpressing the fusion protein Tat-Flag. In addition, 1084i Tat can activate LTR and NF-κB more efficiently than NL4-3 Tat. In analyses of the activities of the truncated forms of Tat, we found that the carboxyl-terminal region of Tat regulates its stability and transactivity. According to our results, we speculated that the differences in stability between B-Tat and C-Tat result in differences in transactivation ability.
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