INHIBITION BY DESFERRIOXAMINE OF IN VITRO REPLICATION OF HIV-1

我们研究过的一些肝细胞癌细胞系 去铁胺(去铁胺；DFX)的综合作用 乙肝病毒，它有一个不寻常的逆转录步在其 复制；这促使我们测试DFX的抗逆转录病毒活性。 对感染HIV-1的H9细胞的重复培养进行了研究。在第7天， 对上清液的编码样本进行了测试。 在这项盲法研究中，DFX抑制p24抗原和 显著降低H9细胞中Gag和env基因的可检测水平 7天后进行培养。抑制作用呈剂量依赖关系；30MU-mDFX 对p24基因表达的影响与187 mU-M AZT(叠氮硫亚胺[AZT])相同； 齐多夫定)(50mU·g/ml)。在不含DFX和AZT的培养基中培养 产生大量的p24，以及Gag和Env的信号 序列呈强阳性。H9细胞存活率在70%以上。 在所有文化中都是在第7天。进行了三个独立的实验， P24的表达也有类似的结果。对GAG和ENV进行了评价 仅在一次实验中可用。 DFX可能通过干扰依赖RNA的DNA来抑制HIV-1 在每个感染周期的早期发生的合成。观察到的 DFX对HIV-1的体外抑制作用提示病毒作用的新机制 抑制力。

Some of the hepatocellular carcinoma lines in which we had studied the effect of deferoxamine (desferrioxamine; DFX) contained integrated hepatitis B virus, which has an unusual reverse transcription step in its replication; this promoted us to test DFX for antiretroviral activity. Duplicate cultures of H9 cells infected with HIV-1 were studied. At day 7, coded samples of supernatants were tested. In this blinded study, DFX inhibited the expression of p24 antigen and substantially reduced detectable levels of gag and env genes in H9 cell cultures after 7 days. The inhibition was dose-dependent; 30 mu-m DFX had the same effect on p24 expression as 187 mu-M AZT (azidothyimidine [AZT]; zidovudine) (50 mu-g/ml). Cultures grown in medium lacking DFX and AZT produced substantial concentrations of p24, and the signals for gag and env sequences were strongly positive. Viability of the H9 cells was above 70% at day 7 in all cultures. Three independent experiments were done, with similar results for p24 expression. Evaluation of gag and env were available only in one experiment. DFX could have inhibited HIV-1 by interfering with the RNA-dependent DNA synthesis that occurs early in each infectious cycle. The observation of in vitro inhibition of HIV-1 by DFX suggests a new mechanism of viral inhibition.