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亚氯酸盐-氧反应产物四氯十氧对HIV传染性的灭活作用

Inactivation of HIV infectivity by the chlorite-oxygen reaction product tetrachlorodecaoxygen.

作者信息

Ennen J, Werner K, Kühne F W, Kurth R

机构信息

Paul-Ehrlich Institute, Langen, Germany.

出版信息

AIDS. 1993 Sep;7(9):1205-12. doi: 10.1097/00002030-199309000-00009.

DOI:10.1097/00002030-199309000-00009
PMID:8216977
Abstract

OBJECTIVE

Since the chlorite-oxygen reaction product tetrachlorodecaoxygen (TCDO) anion complex promotes efficaciously tissue repair and has antibacterial activity, our aim was to determine the effects of TCDO on the replication of HIV and on the infectivity of free HIV particles.

DESIGN

The effects of TCDO on cellular HIV replication machinery and the consequences of TCDO for infectivity of HIV virions were evaluated.

METHODS

Virus yields in supernatants of TCDO-supplemented cultures of HIV-infected cells or virus infectivity in TCDO-treated virus stocks were quantified by titration assays and then calculating the 50% tissue culture infectious dose.

RESULTS

First, TCDO did not affect the replication of HIV in persistently infected lymphocytic and monocytic cell lines or in peripheral blood mononuclear cells. Second, supplementation of HIV stocks with TCDO markedly decreased the infectivity of HIV particles in a concentration dependent manner. Third, the binding of gp120 envelope glycoprotein of HIV-1 to cells is blocked by pre-incubation with TCDO. Fourth, the inhibition of HIV replication by the reverse transcriptase inhibitor 3'-azido-3'-deoxythymidine (zidovudine) in de novo infected cell cultures was not affected by the simultaneous addition of TCDO. However, the delayed virus spread of HIV in cultures in the presence of suboptimal concentrations of zidovudine could significantly be blocked by the simultaneous addition of TCDO. Fifth, TCDO failed to induce the chromosomally integrated HIV-1 provirus in the T-lymphoma cell line ACH2.

CONCLUSIONS

TCDO appears to inactivate HIV particles directly, but has no influence on the intracellular replicative machinery of HIV. Our results suggest that a clinical evaluation of the TCDO complex as chemotherapy for HIV infection and full-blown AIDS should be considered, particularly in patients concomitantly receiving zidovudine.

摘要

目的

由于亚氯酸盐 - 氧反应产物四氯十氧(TCDO)阴离子复合物能有效促进组织修复并具有抗菌活性,我们的目的是确定TCDO对HIV复制及游离HIV颗粒感染性的影响。

设计

评估TCDO对细胞内HIV复制机制的影响以及TCDO对HIV病毒体感染性的作用。

方法

通过滴定测定法对添加TCDO的HIV感染细胞培养上清液中的病毒产量或经TCDO处理的病毒储备液中的病毒感染性进行定量,然后计算50%组织培养感染剂量。

结果

首先,TCDO不影响HIV在持续感染的淋巴细胞和单核细胞系或外周血单核细胞中的复制。其次,向HIV储备液中添加TCDO以浓度依赖方式显著降低HIV颗粒的感染性。第三,HIV-1的gp120包膜糖蛋白与细胞的结合可被TCDO预孵育阻断。第四,在新感染的细胞培养物中,逆转录酶抑制剂3'-叠氮-3'-脱氧胸苷(齐多夫定)对HIV复制的抑制不受同时添加TCDO的影响。然而,在存在次优浓度齐多夫定的培养物中,HIV延迟的病毒传播可被同时添加TCDO显著阻断。第五,TCDO未能在T淋巴瘤细胞系ACH2中诱导染色体整合的HIV-1前病毒。

结论

TCDO似乎直接使HIV颗粒失活,但对HIV的细胞内复制机制没有影响。我们的结果表明,应考虑对TCDO复合物作为HIV感染和晚期艾滋病化疗药物进行临床评估,特别是对于同时接受齐多夫定治疗的患者。

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