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一种用于体外评估干扰素及其他药物抗病毒活性的新型携带1型人类免疫缺陷病毒的宿主细胞系统。

A new contained human immunodeficiency virus type 1 host cell system for evaluation of antiviral activities of interferons and other agents in vitro.

作者信息

Moussazadeh M, Hua J, Sidhu M K, Zhao X X, Fitzgibbon J E, Liao M J, Rashidbaigi A

机构信息

Interferon Sciences Inc., New Brunswick, NJ 08901, USA.

出版信息

Antiviral Res. 1999 Jul;42(3):177-87. doi: 10.1016/s0166-3542(99)00014-5.

Abstract

HIV-host infection systems in vitro are important in the pre-clinical assessment of anti-retroviral drug activity. The present report describes the development of a new HIV-host model comprised of an epithelial cell line of HeLa lineage (HeLa-1), transfected with expression vectors bearing tat and rev (TART) genes of HIV-1 as well as the CD4 receptor gene, and HIV-1(delta Tat/Rev), a biologically contained strain of HIV-1 deleted in tat and rev. Measurement of infectivity, by syncytium formation and reverse transcriptase assay, revealed that HeLa-1 is infected with HIV-1(deltaTat/Rev). This virus failed to productively infect the TART-deficient CD4-positive HeLa cells, confirming its contained, non-infectious nature. The HeLa-1/HIV-1deltaTat/Rev system was used to measure the anti-retroviral activity of a human leukocyte-derived interferon (IFN-alphan3) preparation, several nucleoside analogs, and protease inhibitors. The HeLa-1/ HIV-1(deltaTat/Rev model provides a biologically contained system for the study of the HIV pathogenesis and the relative and combined therapeutic effects of anti-retroviral agents in vitro.

摘要

体外的HIV-宿主感染系统在抗逆转录病毒药物活性的临床前评估中很重要。本报告描述了一种新的HIV-宿主模型的构建,该模型由HeLa谱系的上皮细胞系(HeLa-1)组成,用携带HIV-1的tat和rev(TART)基因以及CD4受体基因的表达载体转染,以及HIV-1(delta Tat/Rev),一种在tat和rev基因缺失的生物安全型HIV-1毒株。通过合胞体形成和逆转录酶测定法测量感染性,结果显示HeLa-1被HIV-1(deltaTat/Rev)感染。这种病毒未能有效感染缺乏TART的CD4阳性HeLa细胞,证实了其生物安全性和非感染性。HeLa-1/HIV-1deltaTat/Rev系统用于测量人白细胞衍生干扰素(IFN-alphan3)制剂、几种核苷类似物和蛋白酶抑制剂的抗逆转录病毒活性。HeLa-1/HIV-1(deltaTat/Rev)模型为体外研究HIV发病机制以及抗逆转录病毒药物的相对和联合治疗效果提供了一个生物安全系统。

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