HIV-1初始传播病毒Vpr基因遗传变异对诱导G2期阻滞及细胞凋亡的影响

doi:10.16288/j.yczz.15-004

遗传 ›› 2015, Vol. 37 ›› Issue (5): 480-486.doi: 10.16288/j.yczz.15-004

HIV-1初始传播病毒Vpr基因遗传变异对诱导G₂期阻滞及细胞凋亡的影响

赵建元^1,2,丁寄葳²,米泽云²,周金明²,魏涛¹,岑山²

1. 北京联合大学应用文理学院,北京 100192;
2. 中国医学科学院医药生物技术研究所,北京 100050

收稿日期:2015-01-04 出版日期:2015-05-20 发布日期:2015-05-20
通讯作者: 岑山,博士,研究员,研究方向：病毒学。E-mail: shancen@hotmail.com;魏涛,硕士,教授,研究方向：病毒学。E-mail: weitao@buu.edu.cn
作者简介:赵建元,硕士研究生,专业方向：病毒学。E-mail: Zjyuan815@163.com
基金资助:
北京联合大学研究生创新基金(编号：12246994501)和国家基金委-加拿大国立卫生研究院研究基金课题(CIHR)合作基金(编号：81361128017)资助

Genetic variance in the HIV-1 founder virus Vpr affects its ability to induce cell cycle G₂ arrest and cell apoptosis

Jianyuan Zhao^{1, 2}, Jiwei Ding², Zeyun Mi², Jinming Zhou², Tao Wei¹, Shan Cen²

1. Department of Food Science, College of Arts & Science of Beijing Union University, Beijing 100192, China;
2. Institute of Medicinal Biotechnology, Chinese Academy of Medical Science and Peking Union Medical School, Beijing 100050, China

Received:2015-01-04 Online:2015-05-20 Published:2015-05-20

摘要/Abstract

摘要： 人免疫缺陷病毒(HIV-1)急性感染过程中,病毒的遗传多样性显著减少,往往只有一株或几株病毒可以建立有效感染,这种病毒被称为初始传播病毒(Transmitted/Founder virus)。病毒蛋白R(Vpr)是HIV-1的辅助蛋白之一,在病毒复制过程中起重要作用。研究初始传播病毒Vpr基因遗传变异与生物学特征对于阐明病毒建立感染的关键环节具有重要意义。文章利用流式细胞术分析了C亚型HIV-1初始传播病毒株与慢性感染株MJ4的 Vpr蛋白诱导细胞G₂期阻滞和细胞凋亡的能力。结果显示,初始传播病毒ZM246和ZM247的Vpr诱导细胞G₂期阻滞和细胞凋亡的能力显著高于慢性感染株MJ4 Vpr。氨基酸序列分析表明,初始传播病毒Vpr在第77、85和94位上存在高频突变。研究结果提示初始传播病毒可能在病毒感染早期,通过Vpr基因的遗传突变,提升病毒诱导细胞停滞G₂期和细胞凋亡的能力,进而促进病毒在宿主体内的复制和传播。

关键词: 人免疫缺陷病毒, 初始传播病毒, 病毒蛋白R(Vpr), 细胞G2 期阻滞, 细胞凋亡

Abstract: In the event of acute infection, only a few HIV-1 viral variants can establish the initial productive clinical infection, and these viral variants are known as transmitted/founder viruses (T/F viruses). As one of the accessory proteins of HIV-1, viral protein R (Vpr) plays an important role in viral replication. Therefore, the characterization of T/F virus Vpr is beneficial to understand how virus replicates in a new host. In this study, flow cytometry was used to analyze the effect of G₂ arrest and cell apoptosis induced by the T/F virus Vpr and the chronic strain MJ4 Vpr. The results showed that the ability of T/F virus ZM246 Vpr and ZM247 Vpr inducing G₂ arrest and cell apoptosis are more potent than the MJ4 Vpr. The comparison of protein sequences indicated that the amino acids of 77, 85 and 94 contain high freqency mutations, suggesting that these sites may be involved in inducing G₂ arrest and cell apoptosis. Taken together, our work suggests that in acute infections, T/F viruses increase the capacity of G₂ arrest and cell apoptosis and promote viral replication and transmission in a new host by Vpr genetic mutation.

Key words: HIV-1, founder virus, Vpr, cell G2 arrest, cell apoptosis

赵建元,丁寄葳,米泽云,周金明,魏涛,岑山. HIV-1初始传播病毒Vpr基因遗传变异对诱导G₂期阻滞及细胞凋亡的影响[J]. 遗传, 2015, 37(5): 480-486.

Jianyuan Zhao, Jiwei Ding, Zeyun Mi, Jinming Zhou, Tao Wei, Shan Cen. Genetic variance in the HIV-1 founder virus Vpr affects its ability to induce cell cycle G₂ arrest and cell apoptosis[J]. HEREDITAS(Beijing), 2015, 37(5): 480-486.

参考文献

[1] Kamiyama T, Miura T, Takeuchi H. His-Trp cation-π interaction and its structural role in anα-helical dimer of HIV-1 Vpr protein . Biophys Chem , 2013, 173-174: 8-14.
[2] Guenzel CA, Hérate C, Benichou S. HIV-1 Vpr-a still "enigmatic multitasker" . Front Microbiol , 2014, 5: 127.
[3] Morellet N, Bouaziz S, Petitjean P, Roques BP. NMR structure of the HIV-1 regulatory protein VPR . J Mol Biol , 2003, 327(1): 215-227.
[4] Zhao LJ, Jian H, Zhu HH. HIV-1 auxiliary regulatory protein Vpr promotes ubiquitination and turnover of Vpr mutants containing the L64P mutation . FEBS Lett , 2004, 563(1-3): 170-178.
[5] Kichler A, Pages JC, Leborgne C, Druillennec S, Lenoir C, Coulaud D, Delain E, Le Cam E, Roques BP, Danos O. Efficient DNA transfection mediated by the C-terminal domain of human immunodeficiency virus type 1 viral protein R . J Virol , 2000, 74(12): 5424-5431.
[6] Sherman MP, De Noronha CMC, Williams SA, Greene WC. Insights into the biology of HIV-1 viral protein R . DNA Cell Biol , 2002, 21(9): 679-688.
[7] Coeytaux E, Coulaud D, Le Cam E, Danos O, Kichler A. The cationic amphipathic α-helix of HIV-1 viral protein R (Vpr) binds to nucleic acids, permeabilizes membranes, and efficiently transfects cells . J Biol Chem , 2003, 278(20): 18110-18116.
[8] Hoshino S, Konishi M, Mori M, Shimura M, Nishitani C, Kuroki Y, Koyanagi Y, Kano S, Itabe H, Ishizaka Y. HIV-1 Vpr induces TLR4/MyD88-mediated IL-6 production and reactivates viral production from latency . J Leukoc Biol , 2010, 87(6): 1133-1143.
[9] Fassati A, Goff SP. Characterization of intracellular reverse transcription complexes of human immunodeficiency virus type 1 . J Virol , 2001, 75(8): 3626-3635.
[10] Fritz JV, Dujardin D, Godet J, Didier P, De Mey J, Darlix JL, Mély Y, de Rocquigny H. HIV-1 Vpr oligomerization but not that of Gag directs the interaction between Vpr and Gag . J Virol , 2010, 84(3): 1585-1596.
[11] Wen XY, Duus KM, Friedrich TD, de Noronha CMC. The HIV1 protein Vpr acts to promote G2 cell cycle arrest by engaging a DDB1 and Cullin4A-containing ubiquitin ligase complex using VprBP/DCAF1 as an adaptor . J Biol Chem , 2007, 282(37): 27046-27057.
[12] Jacotot E, Ravagnan L, Loeffler M, Ferri KF, Vieira HLA, Zamzami N, Costantini P, Druillennec S, Hoebeke J, Briand JP, Irinopoulou T, Daugas E, Susin SA, Cointe D, Xie ZH, Reed JC, Roques BP, Kroemer G. The HIV-1 viral protein R induces apoptosis via a direct effect on the mitochondrial permeability transition pore . J Exp Med , 2000, 191(1): 33-46.
[13] Li G, Bukrinsky M, Zhao RY. HIV-1 viral protein R (Vpr) and its interactions with host cell . Curr HIV Res , 2009, 7(2): 178-183.
[14] Le Rouzic E, Benichou S. The Vpr protein from HIV-1: distinct roles along the viral life cycle . Retrovirology , 2005, 2(1): 11.
[15] Deniaud A, Brenner C, Kroemer G. Mitochondrial membrane permeabilization by HIV-1 Vpr . Mitochondrion , 2004, 4(2-3): 223-233.
[16] Wang B, Ge YC, Palasanthiran P, Xiang SH, Ziegler J, Dwyer DE, Randle C, Dowton D, Cunningham A, Saksena NK. Gene defects clustered at the C-terminus of the vpr gene of HIV-1 in long-term nonprogressing mother and child pair: in vivo evolution of vpr quasispecies in blood and plasma . Virology , 1996, 223(1): 224-232.
[17] Lum JJ, Cohen OJ, Nie ZL, Weaver JG, Gomez TS, Yao XJ, Lynch D, Pilon AA, Hawley N, Kim JE, Chen ZX, Montpetit M, Sanchez-Dardon J, Cohen EA, Badley AD. Vpr R77Q is associated with long-term nonprogressive HIV infection and impaired induction of apoptosis . J Clin Invest , 2003, 111(10): 1547-1554.
[18] Keele BF. Identifying and characterizing recently transmitted viruses . Curr Opin HIV AIDS , 2010, 5(4): 327-334.
[19] Sagar M, Laeyendecker O, Lee S, Gamiel J, Wawer MJ, Gray RH, Serwadda D, Sewankambo NK, Shepherd JC, Toma J, Huang W, Quinn TC. Selection of HIV variants with signature genotypic characteristics dur

编辑推荐

Metrics

www.chinagene.cn
备案号：京ICP备09063187号-4
总访问:,今日访问:,当前在线:

HIV-1初始传播病毒Vpr基因遗传变异对诱导G₂期阻滞及细胞凋亡的影响

Genetic variance in the HIV-1 founder virus Vpr affects its ability to induce cell cycle G₂ arrest and cell apoptosis

PDF (PC)

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 13

编辑推荐

Metrics

[1]	王翠玲, 刘信燚, 王亚会, 张争, 王治东, 周钢桥. MCM2通过抑制p53信号通路促进胆管癌细胞的增殖、迁移和侵袭[J]. 遗传, 2022, 44(3): 230-244.
[2]	秦中勇, 石晓, 曹平平, 褚鹰, 管蔚, 杨楠, 程禾, 孙玉洁. 细胞凋亡反应中NOXA基因启动子发挥增强子功能调节BCL2基因表达[J]. 遗传, 2020, 42(11): 1110-1121.
[3]	余同露,蔡栋梁,朱根凤,叶晓娟,闵太善,陈红岩,卢大儒,陈浩明. CSN4基因干扰对乳腺癌MDA-MB-231细胞增殖和凋亡的影响[J]. 遗传, 2019, 41(4): 318-326.
[4]	赵建元,丁寄葳,米泽云,魏涛,岑山. 人类免疫缺陷病毒初始传播病毒的鉴别及其表型特征[J]. 遗传, 2015, 37(5): 419-425.
[5]	毕丹,徐扬,逄越,李庆伟. 质膜组分磷脂酰丝氨酸外翻的分子调控机制[J]. 遗传, 2015, 37(2): 140-147.
[6]	张蕾, 隋御, 王婷, 李利坚, 李元杰, 金彩霞, 徐方. hMMS2基因对结肠癌细胞耐药逆转的影响[J]. 遗传, 2014, 36(4): 346-353.
[7]	王师尧，金巍娜，吴丹. 青少年型神经元蜡样脂褐质沉积病(JNCL)的发病机制[J]. 遗传, 2009, 31(8): 779-784.
[8]	马向东，马兴，吴小明，陈必良，王德堂 . 胚胎神经管缺陷大鼠模型差异基因的表达[J]. 遗传, 2009, 31(3): 280-284.
[9]	郭芬，刘兆宇，李月琴，李弘剑，周天鸿. Prosaposin对细胞增殖和凋亡的调控及其分子机制[J]. 遗传, 2009, 31(12): 1226-1232.
[10]	付浩，赵丹懿，孙秀菊，滑君，阎杨，邱广蓉，尚超，富伟能，孙开来. B-RAF基因特异的siRNA干扰对胃癌BGC823细胞的影响[J]. 遗传, 2007, 29(5): 537-537―540.
[11]	王琳，梁旭方，廖婉琴，周天鸿. 斑马鱼胚胎发育中细胞凋亡的研究进展[J]. 遗传, 2006, 28(8): 1009-1014.
[12]	王振兴，王璞，姚玲，曾智东，徐汉福，段军，王根洪，夏庆友. 家蚕细胞凋亡相关基因BmICAD的克隆、序列和功能分析及其在精巢中特异表达的初步研究[J]. 遗传, 2006, 28(7): 838-844.
[13]	李艳凤，张强，朱大海. 泛素介导的蛋白质降解与肿瘤发生[J]. 遗传, 2006, 28(12): 1591-1591~1596.