Susceptibilities of zidovudine-susceptible and -resistant human immunodeficiency virus isolates to antiviral agents determined by using a quantitative plaque reduction assay
Susceptibilities of zidovudine-susceptible and -resistant human immunodeficiency virus isolates to antiviral agents determined by using a quantitative plaque reduction assay
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使用定量空斑减少测定法测定齐多夫定敏感和耐药的人类免疫缺陷病毒分离株对抗病毒药物的敏感性
DOI：
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发表时间：
1990
影响因子：
4.9
通讯作者：
D. Richman
中科院分区：
文献类型：
--
作者：
B. Larder;'. B. Chesebro;D. Richman
基于用人类免疫缺陷病毒（HIV）的组织培养适应株感染T细胞类淋巴母细胞系的常规测定法已得到很好的建立，并已成功地用于发现HIV复制的有效抑制剂。在这份报告中，我们表明，这样的检测是不容易应用于测试的antibiabilities临床HIV分离株的抑制剂，因为复制率和细胞毒性的差异，从而表明，传统的HIV检测应谨慎使用时，齐多夫定临床分离株的敏感性进行评估。通过测定该系统中HIV对大量抑制剂的亲和性，验证了基于CD 4 + HeLa细胞单层中空斑减少的测定。一般来说，50%抑制剂量的HIV 1型和2型菌株来自空斑减少数据与敏感性数据通过使用传统的检测与T细胞系。先前确定的齐多夫定耐药的HIV分离株的亲和性一大组抑制剂，包括nonucleosides，如干扰素和可溶性CD 4，通过使用在CD 4 + HeLa细胞中的空斑减少试验进行了测试。令人惊讶的是，观察到了极窄范围的交叉抗性;交叉抗性限于含有3 '-叠氮基的核苷类似物。这些数据指出了使用抑制剂组合来延迟耐药性出现的方法。
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 nonucleosides, 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.
影响因子：
56.9
作者：
LARDER, BA;DARBY, G;RICHMAN, DD
通讯作者：
RICHMAN, DD
影响因子：
56.9
作者：
CHENGMAYER, C;SETO, D;LEVY, JA
通讯作者：
LEVY, JA