Volsky D J, Li G, Hamblet N, Volsky B, Decker R S, Pellegrino M G, Potash M J
Molecular Virology Laboratory, St Luke's/Roosevelt Hospital Center, New York, NY.
Antiviral Res. 1992 Apr;17(4):335-47. doi: 10.1016/0166-3542(92)90028-4.
Evaluation of the activities of antiretroviral agents and an immunoregulatory compound has been made using two models of HIV-1 infection and three measurements of virus expression. Acute infection of Jurkat cells or chronic/inducible infection in U1.1 cells was monitored at multiple time points after drug treatment. The 50% effective concentrations (EC50) of the HIV-1 inhibitors suramin, 3'-azido-3'-deoxythymidine (AZT), and 2',3'-dideoxycytidine, as measured by HIV-1 RNA hybridization in Jurkat cells two days after infection, were comparable to EC50 values obtained in parallel measurements of extracellular p24 levels and percent HIV-1 IF-positive cells. However, these measurements diverged: at seven days after infection the EC50 of AZT was greater than 10 microM when intracellular HIV-1 RNA was assayed, 0.2 microM by IF, and 0.03 microM by p24 assay. Human thymic humoral factor displayed no direct inductive activity in chronic HIV-1 infection in U1.1 cells, while phorbol ester and lymphocyte supernatants induced all parameters. These observations warrant care when interpreting results of only a single assay and suggest that definitive assay of HIV-1 infection requires measurements of multiple parameters of virus expression.
利用两种HIV-1感染模型和三种病毒表达测量方法，对抗逆转录病毒药物和一种免疫调节化合物的活性进行了评估。在药物处理后的多个时间点监测Jurkat细胞的急性感染或U1.1细胞中的慢性/诱导性感染。通过感染后两天在Jurkat细胞中进行HIV-1 RNA杂交测量，HIV-1抑制剂苏拉明、3'-叠氮-3'-脱氧胸苷（AZT）和2',3'-二脱氧胞苷的50%有效浓度（EC50）与通过细胞外p24水平和平行测量的HIV-1 IF阳性细胞百分比获得的EC50值相当。然而，这些测量结果有所不同：感染后七天，当检测细胞内HIV-1 RNA时，AZT的EC50大于10 microM，通过IF检测为0.2 microM，通过p24检测为0.03 microM。人胸腺体液因子在U1.1细胞的慢性HIV-1感染中未显示出直接诱导活性，而佛波酯和淋巴细胞上清液可诱导所有参数。这些观察结果表明，在解释仅单一检测的结果时需谨慎，并表明对HIV-1感染进行明确检测需要测量病毒表达的多个参数。
