Role of Nup98 in nuclear entry of human immunodeficiency virus type 1 cDNA
Role of Nup98 in nuclear entry of human immunodeficiency virus type 1 cDNA
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DOI：
10.1016/j.micinf.2004.04.002
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发表时间：
2004-07-01
影响因子：
5.8
通讯作者：
Koyanagi, Y
中科院分区：
文献类型：
--
作者：
Ebina, H;Aoki, J;Koyanagi, Y
人类免疫缺陷病毒1型（HIV-1），像其他慢病毒一样，可以感染非分裂细胞。慢病毒很可能已经进化出一种核输入策略，通过由核孔蛋白（Nup）形成的核孔复合物（NPC）输入HIV-1 cDNA和病毒蛋白复合物。在这项研究中，我们发现，综合和2LTR，但不是全长形式的HIV-1 cDNA的合成明显受损，通过水泡性口炎病毒基质蛋白（VSV M），抑制蛋白，通过结合Nup 98的苯丙氨酸-甘氨酸（FG）重复区转导文化。整合和2LTR DNA与VSV M的合成损伤恢复异位过表达的Nup 98。通过小干扰RNA（siRNA）技术使用Nup 98缺失的NPC进行的一系列实验显示NPC结构和一些功能的特异性损伤，包括HIV-1 cDNA的核输入。我们的研究结果表明NPC上的Nup 98特异性地参与了HIV-1进入后HIV-1 cDNA的核进入。(C)2004年，Elsevier SAS。All rights reserved.
Human immunodeficiency virus type 1 (HIV-1), like other lentiviruses, can infect non-dividing cells. The lentiviruses are most likely to have evolved a nuclear import strategy to import HIV-1 cDNA and viral protein complex through the nuclear pore complex (NPC) formed by nucleoporin proteins (Nup). In this study, we found that synthesis of integrated and 2LTR but not full-length form of HIV-1 cDNA was clearly impaired in culture via transduction of vesicular stomatitis virus matrix protein (VSV M), an inhibitor protein, through binding to the phenylalanine-glycine (FG) repeat region of Nup98. The impairment of synthesis of integrated and 2LTR DNA with VSV M was restored by ectopic overexpression of Nup98. A series of experiments using Nup98-depleted NPC by the small interfering RNA (siRNA) technique showed specific impairment of NPC structure and some functions, including nuclear import of HIV-1 cDNA. Our results suggest that Nup98 on the NPC specifically participates in the nuclear entry of HIV-1 cDNA following HIV-1 entry. (C) 2004 Elsevier SAS. All rights reserved.