The 57th amino acid conveys the differential subcellular localization of human immunodeficiency virus-1 Tat derived from subtype B and C
The 57th amino acid conveys the differential subcellular localization of human immunodeficiency virus-1 Tat derived from subtype B and C
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第57个氨基酸传达源自B和C亚型的人类免疫缺陷病毒1 Tat的差异亚细胞定位
DOI：
10.1007/s11262-015-1267-9
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发表时间：
2016
期刊：
影响因子：
1.6
通讯作者：
Kong Xiaohong
中科院分区：
文献类型：
--
作者：
Zhao Xuechao;Qian Lingyu;Qi Di;Zhou Deyu;Shen Wenyuan;Liu Yu;Liu Chang;Kong Xiaohong
多功能反式激活蛋白 Tat 是 HIV-1 复制的本质调节蛋白，在 HIV-1 感染的发病机制中发挥作用。目前关于HIV-1 Tat的实验研究较多集中在B亚型，对C-Tat亚型的研究很少。鉴于进化枝特异性Tat蛋白的氨基酸变异，我们假设氨基酸差异导致Tat蛋白的功能差异。在本研究中，我们记录了来自赞比亚儿科患者的 B 亚型 NL4-3 Tat 和 C 亚型分离 HIV1084i Tat 通过过表达融合蛋白 Tat-EGFP 表现出明显的核定位。有趣的是，1084i Tat 显示出均匀的核分布，而 NL4-3 Tat 主要位于核仁中。第57个氨基酸在B-Tat（精氨酸）和C-Tat（丝氨酸）之间高度保守，位于Tat的基本结构域中，并在此亚细胞定位中发挥重要作用。同时，我们发现57位点的精氨酸替换为丝氨酸会降低HIV-1 LTR启动子的Tat反式激活。
The multifunctional transactivator Tat protein is an essentially regulatory protein for HIV-1 replication and it plays a role in pathogenesis of HIV-1 infection. At present, numerous experimental studies about HIV-1 Tat focus on subtype B, very few has been under study of subtype C-Tat. In view of the amino acid variation of the clade-specific Tat proteins, we hypothesized that the amino acid difference contributed to differential function of Tat proteins. In the present study, we documented that subtype B NL4-3 Tat and subtype C isolate HIV1084i Tat from pediatric patient in Zambia exhibited distinct nuclear localization by over-expressing fusion protein Tat-EGFP. Interestingly, 1084i Tat showed uniform nuclear distribution, whereas NL4-3 Tat primarily localized in nucleolus. The 57th amino acid, highly conserved between B-Tat (arginine) and C-Tat (serine), is located in the basic domain of Tat, and played an important role in this subcellular localization. Meanwhile, we found that substitution of arginine to serine at the site 57 decreases Tat transactivation of the HIV-1 LTR promoter.