Anti-human immunodeficiency virus 1 (HIV-1) activities of 3-deazaadenosine analogs: increased potency against 3-azido-3-deoxythymidine-resistant HIV-1 strains.

机译：3-deazaadenosine类似物的抗人类免疫缺陷病毒1（HIV-1）活性：抗3-叠氮基3-脱氧胸苷的HIV-1菌株的效力增强。

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3-Deazaadenosine (DZA), 3-deaza-(+/-)-aristeromycin (DZAri), and 3-deazaneplanocin A (DZNep) are powerful modulators of cellular processes. When tested against H9 cells infected acutely with two different strains of human immunodeficiency virus 1 (HIV-1) and in the chronically infected monocytoid cell lines U1 and THP-1, the 3-deazanucleosides caused a marked reduction in p24 antigen production. Similar reductions in p24 antigen were seen in phytohemagglutinin-stimulated peripheral blood mononuclear cells infected with clinical HIV-1 isolates. Strikingly, in comparing the therapeutic indices between the paired pre- and post-3'-azido-3'-deoxythymidine (AZT) treatment HIV-1 isolates, DZNep and neplanocin A showed an increase of 3- to 18-fold in their potency against AZT-resistant HIV-1 isolates. In H9 cells treated with DZNep and DZAri, the formation of triphosphate nucleotides of DZNep and DZAri was observed. The mode of action of DZNep and DZAri appears complex, at least in part, at the level of infectivity as shown by decreases in syncytia formation in HIV-1-infected H9 cells and at the level of transcription as both drugs inhibited the expression of basal or tat-induced HIV-1 long terminal repeat chloramphenicol acetyltransferase activity in stably transfected cell lines. Since DZNep induced in H9 cells a rapid expression of nuclear binding factors that recognize the AP-1 transcription site, the anti-HIV-1 activity of the DZA analogs could partly be the induction of critical factors in the host cells. Thus, the 3-deazanucleoside drugs belong to an unusual class of anti-HIV-1 drugs, which may have therapeutic potential, in particular against AZT-resistant strains.

机译：3-Deazaadenosine（DZA），3-deaza-（+/-）-arasteromycin（DZAri）和3-deazaneplanocin A（DZNep）是细胞过程的强大调节剂。当针对用两种不同株的人类免疫缺陷病毒1（HIV-1）急性感染的H9细胞进行测试时，以及在慢性感染的单核细胞样细胞系U1和THP-1中，3-脱氮核苷导致p24抗原产生显着减少。在被临床HIV-1分离株感染的植物血凝素刺激的外周血单核细胞中，p24抗原的减少量相似。令人惊讶的是，在比较配对的3'前和后3'-叠氮基3'-脱氧胸苷（AZT）治疗HIV-1分离株之间的治疗指数时，DZNep和neplanocin A的效力提高了3到18倍抗AZT的HIV-1分离株。在用DZNep和DZAri处理的H9细胞中，观察到DZNep和DZAri的三磷酸核苷酸的形成。 DZNep和DZAri的作用模式至少在部分感染性方面表现出复杂性，如感染HIV-1的H9细胞合胞体形成减少和转录水平所显示，因为这两种药物均抑制了基底膜的表达或tat诱导的在稳定转染的细胞系中的HIV-1长末端重复氯霉素乙酰转移酶活性。由于DZNep在H9细胞中诱导了识别AP-1转录位点的核结合因子的快速表达，因此DZA类似物的抗HIV-1活性可能部分是宿主细胞中关键因子的诱导。因此，3-脱氮核苷药物属于一类不常见的抗HIV-1药物，可能具有治疗潜力，尤其是针对AZT耐药菌株。

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期刊名称 Proceedings of the National Academy of Sciences of the United States of America
作者
D L Mayers; J A Mikovits; B Joshi; I K Hewlett; J S Estrada; A D Wolfe; G E Garcia; B P Doctor; D S Burke; R K Gordon;
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年(卷),期 1995(92),1
年度 1995
页码 215–219
总页数 5
原文格式 PDF
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1. Anti-human immunodeficiency virus 1 (HIV-1) activities of 3-deazaadenosine analogs: increased potency against 3'-azido-3'-deoxythymidine-resistant HIV-1 strains. [J] . Mayers DL, Mikovits JA, Joshi B, Proceedings of the National Academy of Sciences of the United States of America . 1995,第1期

机译：3-deazaadenosine类似物的抗人类免疫缺陷病毒1（HIV-1）活性：抗3'-叠氮基3'-脱氧胸苷的HIV-1菌株的效力增强。
2. Anti-human immunodeficiency virus type 1 (HIV-1) activity of 2'-fluoro-2',3'-dideoxyarabinosyladenine (F-ddA) used in combination with other mechanistically diverse inhibitors of HIV-1 replication. [J] . Buckheit RW Jr, Russell JD, Pallansch LA, Antiviral chemistry & chemotherapy . 1999,第3期

机译：2'-氟-2'，3'-二脱氧阿拉伯糖基腺嘌呤（F-ddA）的抗人免疫缺陷病毒1型（HIV-1）活性与HIV-1复制的其他机制多样的抑制剂结合使用。
3. Anti-Human Immunodeficiency Virus Type 1 (HIV-1) Activity of Lectins from Narcissus Species. [J] . Lopez S, Bastida J, Este JA, Planta medica: Natural products and medicinal plant research . 2003,第2期

机译：水仙物种凝集素的抗人免疫缺陷病毒1型（HIV-1）活性。
4. Simultaneous extraction of human immunodeficiency virus type 1 (HIV-1) and hepatitis C virus (HCV) RNA with the M1000 apparatus does not impair the measurement of the viral load of both viruses when tested by using the LCx PCR system [C] . T. Bourlet, S. Thamm, S. Pillet, European Congress of Virology . 2004

机译：通过使用LCX PCR系统测试，同时提取人免疫缺陷病毒类型1（HIV-1）和丙型肝炎病毒（HCV）RNA，不会损害两种病毒的病毒载量的测量
5. Do nucleoside analog-resistance mutations increase the fidelity of human immunodeficiency virus type-1 (HIV-1) reverse transcriptase? [D] . Curr, Kenneth Andrew. 2003

机译：核苷类似物抗性突变是否增加了人类1型免疫缺陷病毒（HIV-1）逆转录酶的保真度？
6. Induction of Anti-Human Immunodeficiency Virus Type 1 (HIV-1) CD8+ and CD4+ T-Cell Reactivity by Dendritic Cells Loaded with HIV-1 X4-Infected Apoptotic Cells [O] . Xiao-Qing Zhao, Xiao-Li Huang, Phalguni Gupta, 2002

机译：载有HIV-1 X4感染的树突状细胞的树突状细胞诱导抗人类免疫缺陷病毒1型（HIV-1）CD8 +和CD4 + T细胞反应性。
7. Anti-human immunodeficiency virus 1 (HIV-1) activities of 3-deazaadenosine analogs: increased potency against 3'-azido-3'-deoxythymidine-resistant HIV-1 strains. [O] . Mayers, D L, Mikovits, J A, Joshi, B, 1995

机译：3-deazaadenosine类似物的抗人免疫缺陷病毒1（HIV-1）活性：抗3'-叠氮基3'-脱氧胸苷的HIV-1菌株的效力增强。

Anti-human immunodeficiency virus 1 (HIV-1) activities of 3-deazaadenosine analogs: increased potency against 3-azido-3-deoxythymidine-resistant HIV-1 strains.

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