SUSCEPTIBILITIES OF ZIDOVUDINE-SUSCEPTIBLE AND ZIDOVUDINE-RESISTANT HUMAN-IMMUNODEFICIENCY-VIRUS ISOLATES TO ANTIVIRAL AGENTS DETERMINED BY USING A QUANTITATIVE PLAQUE REDUCTION ASSAY
SUSCEPTIBILITIES OF ZIDOVUDINE-SUSCEPTIBLE AND ZIDOVUDINE-RESISTANT HUMAN-IMMUNODEFICIENCY-VIRUS ISOLATES TO ANTIVIRAL AGENTS DETERMINED BY USING A QUANTITATIVE PLAQUE REDUCTION ASSAY
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DOI：
10.1128/aac.34.3.436
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发表时间：
1990-03-01
影响因子：
4.9
通讯作者：
RICHMAN, DD
中科院分区：
文献类型：
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作者：
LARDER, BA;CHESEBRO, B;RICHMAN, DD
基于组织培养适应的人类免疫缺陷病毒（HIV）株感染t细胞淋巴母细胞样系的常规检测方法已经建立，并已成功用于发现HIV复制的有效抑制剂。在本报告中，我们表明，由于复制率和细胞毒性的差异，这种检测方法不容易用于检测临床HIV分离株对抑制剂的敏感性，因此，在评估临床分离株对齐多夫定的敏感性时，应谨慎使用传统的HIV检测方法。通过确定HIV对该系统中大量抑制剂的敏感性，一项基于CD4+ HeLa细胞单层斑块减少的检测得到了验证。总的来说，根据斑块减少数据得出的50%的HIV 1型和2型毒株抑制剂量与使用常规t细胞系测定获得的易感性数据很好地一致。先前鉴定的齐多夫定耐药HIV分离株对大量抑制剂（包括非核苷类，如干扰素和可溶性CD4）的敏感性，通过在CD4+ HeLa细胞中使用斑块减少试验进行了测试。令人惊讶的是，观察到的交叉阻力范围非常窄；交叉抗性仅限于含有3”-叠氮基的核苷类似物。这些数据为使用联合抑制剂延缓耐药性的出现指明了道路。
Conventional assays based on infection of T-cell lymphoblastoid lines with tissue culture-adapted strains of human immunodeficiency virus (HIV) are well established and have been used successfully to discover potent inhibitors of HIV replication. In this report we show that such assays are not easily applied to testing the susceptibilities of clinical HIV isolates to inhibitors because of differences in replication rates and cytotoxicity, thus demonstrating that conventional HIV assays should be used with caution when the zidovudine susceptibility of clinical isolates is assessed. An assay based on plaque reduction in CD4+ HeLa cell monolayers was validated by determining susceptibilities of HIV to a large number of inhibitors in this system. In general, 50% inhibitory doses for HIV type 1 and 2 strains derived from plaque reduction data were in good agreement with susceptibility data obtained by using conventional assays with T-cell lines. The susceptibilities of previously identified zidovudine-resistant HIV isolates to a large group of inhibitors, including nonnucleosides, such as interferons and soluble CD4, were tested by using a plaque reduction assay in CD4+ HeLa cells. Surprisingly, an extremely narrow range of cross resistance was observed; cross resistance was limited to nucleoside analogs containing a 3''-azido group. These data point the way to the use of combinations of inhibitors to delay the appearance of drug resistance.