中国新药杂志

作用于mRNA编辑酶催化多肽样蛋白3G的HIV-1逆转录抑制剂研究进展

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李俊洁 ¹ , 罗荣华 ² , 杨柳萌 ² , 王婷 ¹ , 马文婕 ¹ , 黄宁 ¹

中国新药杂志 | 综述 2021,30(20): 1855-1860

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中国新药杂志 |综述 2021 , 30 (20) : 1855 -1860

作用于mRNA编辑酶催化多肽样蛋白3G的HIV-1逆转录抑制剂研究进展

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李俊洁¹, 罗荣华², 杨柳萌², 王婷¹, 马文婕¹, 黄宁¹

作者信息

¹昆明医科大学基础医学院药理学系，昆明　650500

²中国科学院昆明动物研究所动物模型与人类疾病重点实验室，昆明　650223

通讯作者:

黄宁，女，副教授，博士，主要从事抗病毒药物研究。E-mail：huangning82@163.com。

马文婕，女，讲师，博士，主要从事中枢神经系统药物研究。E-mail：mwj9598@163.com。

作者简介:

李俊洁，女，硕士研究生，主要从事抗病毒药物研究。E-mail：15736990791@163.com。

Research progress in HIV reverse transcriptional inhibitors acting on apoliprotein B mRNA-editing enzyme catalytic polypetide protein

Jun-jie LI¹, Rong-hua LUO², Liu-meng YANG², Ting WANG¹, Wen-jie MA¹, Ning HUANG¹

Affiliations

¹School of Basic Medical, Kunming Medical University, Kunming 650500, China

²Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China

出版时间: 2021-10-30

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摘要

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mRNA编辑酶催化多肽样蛋白3G（A3G）属于固有免疫家族成员，具有胞嘧啶脱氨酶活性，能通过与核衣壳蛋白基因（Gag）或病毒RNA的核衣壳（NC）域的相互作用包装入子代病毒。在人类免疫缺陷病毒1型（HIV-1）逆转录过程中，A3G使胞嘧啶脱氨基，在DNA负链中引入尿嘧啶，导致病毒的过度突变，发挥抗病毒作用。除此之外，A3G通过包装成病毒粒子发挥抗HIV-1的作用。HIV-1的辅助调节蛋白病毒感染因子（Vif）可以通过泛素-蛋白酶体系统来拮抗A3G的抑制HIV-1的作用。因此，上调A3G的表达或是抑制Vif对A3G的拮抗作用可能成为HIV-1感染治疗的新有效方法。

关键词

病毒HIV-1颗粒 / mRNA编辑酶催化多肽样蛋白3G / 逆转录 / 抗HIV-1药物 / 辅助蛋白病毒感染因子

Abstract

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Apoliprotein B mRNA-editing enzyme catalytic polypetide protein (A3G) is a member of the innate immune family. It has cytosine deaminase activity and can be packaged into progeny viruses through interaction with Gag protein or the nucleocapsid domain of viral RNA. In the process of HIV-1 reverse transcription, A3G deaminates cytosine and introduces uracil into the minus strand of DNA, resulting in excessive mutation of the virus and exerting antiviral effects. In addition, A3G plays an anti-HIV-1 role by packaging itself into virions. HIV-1 co-regulatory protein Vif can antagonize A3G inhibition of HIV-1 through the ubiquitin-proteasome system. Therefore, up-regulating the expression of A3G or inhibiting the antagonistic effect of Vif on A3G may become a new effective method for the treatment of HIV-1 infection.

Key words

virus HIV-1 particles / apoliprotein B mRNA-editing enzyme catalytic polypetide protein / reverse transcription / anti-HIV-1 drugs / accessory protein viral infectivity factor

引用本文

李俊洁, 罗荣华, 杨柳萌, 王婷, 马文婕, 黄宁. 作用于mRNA编辑酶催化多肽样蛋白3G的HIV-1逆转录抑制剂研究进展. 中国新药杂志, 2021 , 30 (20) : 1855 -1860 .

Jun-jie LI, Rong-hua LUO, Liu-meng YANG, Ting WANG, Wen-jie MA, Ning HUANG. Research progress in HIV reverse transcriptional inhibitors acting on apoliprotein B mRNA-editing enzyme catalytic polypetide protein[J]. Chinese Journal of New Drugs, 2021 , 30 (20) : 1855 -1860 .

基金

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国家自然科学基金资助项目(81660612)
云南省基础应用研究-昆医联合专项(2017FE467-127; 2017FE468-135)
昆明医科大学百名中青年学术技术骨干项目(60117190441)

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参考文献引证文献

排序方式：

[1]

HUANG N, WU MY, ZHENG CB, et al. The depolymerized fucosylated chondroitin sulfate from sea cucumber potently inhibits HIV replication via interfering with virus entry[J]. Carbohydr Res, 2013, 380(10): 64-69.

[2]

HUANG N, WANG Q, YANG LM, et al. Anti HIV-1 agents 7. Discovery of 1-hydroxy-4-chloro-9, 10-anthraquinone derivatives as new HIV-1 inhibitors in vitro[J]. Lett Drug Des Disco, 2011, 8(7): 602-605.

[3]

RAN JQ, HUANG N, XU H, et al. Anti HIV-1 agents 5: synthesis and anti-HIV-1 activity of some N-arylsulfonyl-3-acetylindoles in vitro[J]. Bioorg Med Chem Lett, 2010, 20(12): 3534-3536.

[4]

LALONDE MS, LOBRITZ MA, RATCLIFF A, et al. Inhibition of both HIV-1 reverse transcription and gene expression by a cyclic peptide that binds the Tat-transactivating response element (TAR) RNA[J]. PLoS Pathog, 2011, 7(5): e1002038.

[5]

PUROHIT V, BALAKRISHNAN M, KIM B, et al. Evidence that HIV-1 reverse transcriptase employs the DNA 3' end-directed primary/secondary RNase H cleavage mechanism during synthesis and strand transfer[J]. J Biol Chem, 2005, 280(49): 40534-40543.

[6]

WANG Z, LUO Y, SHAO Q, et al. Heat-Stable molecule derived from streptococcus cristatus induces APOBEC3 expression and inhibits HIV-1 replication[J]. PLoS ONE, 2014, 9(8): e106078.

[7]

RAUSCH JW, LE GRICE SF. ‘Binding, bending and bonding’: polypurine tract-primed initiation of plus-strand DNA synthesis in human immunodeficiency virus[J]. Int J Biochem Cell Biol, 2004, 36(9): 1752-1766.

[8]

SHARMA S, PATNAIK SK, TAGGART RT, et al. The double-domain cytidine deaminase APOBEC3G is a cellular site-specific RNA editing enzyme[J]. Sci Rep, 2016, 6(1): 39100.

[9]

PAN Y, SUN Z, MAITI A, et al. Nanoscale characterization of interaction of APOBEC3G with RNA[J]. Biochemistry, 2017, 56(10): 1473-1481.

[10]

GHIMIRE D, RAI M, GAUR R. Novel host restriction factors implicated in HIV-1 replication[J]. J Gen Virol, 2018, 99(4): 435-446.

[11]

ZHANG S, ZHONG L, CHEN B, et al. Identification of an HIV-1 replication inhibitor which rescues host restriction factor APOBEC3G in Vif-APOBEC3G complex[J]. Antiviral Res, 2015, 122(10): 20-27.

[12]

WANG X, AO Z, CHEN L, et al. The cellular antiviral protein APOBEC3G interacts with HIV-1 reverse transcriptase and inhibits its function during viral replication[J]. J Virol, 2012, 86(7): 3777-3786.

[13]

ZIEGLER SJ, LIU C, LANDAU M, et al. Insights into DNA substrate selection by APOBEC3G from structural, biochemical, and functional studies[J]. PLoS One, 2018, 13(3): e0195048.

[14]

MORSE M, HUO R, FENG Y, et al. Dimerization regulates both deaminase-dependent and deaminase-independent HIV-1 restriction by APOBEC3G[J]. Nat Commun, 2017, 8(1): 597.

[15]

LI L, LIANG D, LI JY, et al. APOBEC3G-UBA2 fusion as a potential strategy for stable expression of APOBEC3G and inhibition of HIV-1 replication[J]. Retrovirology, 2008, 5(1): 72.

[16]

TING P, ZHENG S, LIYANG W, et al. USP49 potently stabilizes APOBEC3G protein by removing ubiquitin and inhibits HIV-1 replication[J]. eLife, 2019, 8: e48318.

[17]

CHEN H, ZHANG R, LUO RH, et al. Anti-HIV Activities and mechanism of 12-O-tricosanoylphorbol-20-acetate, a novel phorbol ester from ostodes katharinae[J]. Molecules, 2017, 22(9): 1498.

[18]

ZHOU M, LUO RH, HOU XY, et al. Synthesis, biological evaluation and molecular docking study of N-(2-methoxyphenyl)-6-((4-nitrophenyl)sulfonyl)benzamide derivatives as potent HIV-1 Vif antagonists[J]. Eur J Med Chem, 2017, 129: 310-324.

[19]

PU C, LUO RH, ZHANG M, et al. Design, synthesis and biological evaluation of indole derivatives as Vif inhibitors[J]. Bioorg Med Chem Lett, 2017, 27(17): 4150-4155.

[20]

SUGIYAMA R, NISHITSUJI H, FURUKAWA A, et al. Heat shock protein 70 inhibits HIV-1 Vif-mediated ubiquitination and degradation of APOBEC3G[J]. J Biol Chem, 2011, 286(12): 10051-10057.

[21]

SUGIYAMA R, ABE M, NISHITSUJI H, et al. Induction of heat-shock protein 70 by prostaglandin A(1) inhibits HIV-1 Vif-mediated degradation of APOBEC3G[J]. Antiviral Res, 2013, 99(3): 307-311.

[22]

MIYAKAWA K, MATSUNAGA S, KANOU K, et al. ASK1 restores the antiviral activity of APOBEC3G by disrupting HIV-1 Vif-mediated counteraction[J]. Nat Commun, 2015, 6(4): 6945.

[23]

PERY E, SHEEHY A, MIRANDA NEBANE N, et al. Redoxal, an inhibitor of de novo pyrimidine biosynthesis, augments APOBEC3G antiviral activity against human immunodeficiency virus type 1[J]. Virology, 2015, 484(10): 276-287.

[24]

ZUO T, LIU D, LV W, et al. Small-molecule inhibition of human immunodeficiency virus type 1 replication by targeting the interaction between Vif and ElonginC[J]. J Virol, 2012, 86(10): 5497-5507.

[25]

HUANG W, ZUO T, JIN H, et al. Design, synthesis and biological evaluation of indolizine derivatives as HIV-1 VIF-ElonginC interaction inhibitors[J]. Mol Divers, 2013, 17(2): 221-243.

[26]

PERY E, SHEEHY A, NEBANE NM, et al. Identification of a novel HIV-1 inhibitor targeting Vif-dependent degradation of human APOBEC3G protein[J]. J Biol Chem, 2015, 290(16): 10504-10517.

[27]

CEN S, PENG ZG, LI XY, et al. Small molecular compounds inhibit HIV-1 replication through specifically stabilizing APOBEC3G[J]. J Biol Chem, 2010, 285(22): 16546-16552.

[28]

KUMAR M, RAWAT P, KHAN SZ, et al. Reciprocal regulation of human immunodeficiency virus-1 gene expression and replication by heat shock proteins 40 and 70[J]. J Mol Biol, 2011, 410(5): 944-958.

[29]

SHRIVASTAVA S, TRIVEDI J, MITRA D. Gene expression profiling reveals Nef induced deregulation of lipid metabolism in HIV-1 infected T cells[J]. Biochem Biophys Res Commun, 2016, 472(1): 169-174.

[30]

PARK RJ, WANG T, KOUNDAKJIAN D, et al. A genome-wide CRISPR screen identifies a restricted set of HIV host dependency factors[J]. Nat Genet, 2017, 49(2): 193-203.

2021年第30卷第20期

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首发时间：2026-10-30
出版时间：2021-10-30

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出版历史

录用日期：2021-06-21

基金

国家自然科学基金资助项目(81660612)

云南省基础应用研究-昆医联合专项(2017FE467-127; 2017FE468-135)

昆明医科大学百名中青年学术技术骨干项目(60117190441)

作者信息

¹昆明医科大学基础医学院药理学系，昆明　650500

²中国科学院昆明动物研究所动物模型与人类疾病重点实验室，昆明　650223

通讯作者:

黄宁，女，副教授，博士，主要从事抗病毒药物研究。E-mail：huangning82@163.com。

马文婕，女，讲师，博士，主要从事中枢神经系统药物研究。E-mail：mwj9598@163.com。

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2种不同金属材料的力学参数

科 Family	属数 Number of genus	种数 Number of species	占总种数比例 Percentage of total species (%)	属 Genus	种数 Number of species	占总种数比例 Percentage of total species (%)
鹅膏菌科Amanitaceae	2	11	5.26	鹅膏菌属 Amanita	10	4.78
小菇科 Mycenaceae	2	12	5.74	丝盖伞属 Inocybe	5	2.39
多孔菌科 Polyporaceae	8	14	6.70	蜡蘑属 Laccaria	5	2.39
红菇科 Russulaceae	3	23	11.00	小皮伞属 Marasmius	6	2.87
				小菇属 Mycena	11	5.26
				光柄菇属 Pluteus	5	2.39
				红菇属 Russula	17	8.13
				栓菌属 Trametes	5	2.39

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