Perno C F, Aquaro S, Rosenwirth B, Balestra E, Peichl P, Billich A, Villani N, Caliò R
Department of Experimental Medicine and Biochemical Sciences, University of Rome Tor Vergata, Italy.
J Leukoc Biol. 1994 Sep;56(3):381-6. doi: 10.1002/jlb.56.3.381.
Because of the importance of macrophages in the pathogenesis of the disease caused by HIV, we investigated the efficacy of various anti-HIV drugs in human primary macrophages acutely or chronically infected by this virus. The results obtained for acutely infected macrophages show that dideoxynucleosides (AZT, ddI, and ddC), interferon-alpha and -gamma, mismatched double-stranded RNA, Tat inhibitor, phosphorothioate antisense, and inhibitors of HIV protease, all significantly inhibit virus replication at concentrations far below those toxic for the cells. However, in macrophages in which proviral DNA is already integrated (chronically infected macrophages), only the three inhibitors of HIV protease induced significant virus inhibition at concentrations 100 or more times higher than those effective in acutely infected macrophages. Treatment of macrophages with macrophage colony-stimulating factor does not affect the anti-HIV efficacy of protease inhibitors. These results suggest that therapeutic strategies with activity for macrophages, including inhibitors of HIV protease, are worth pursuing in patients with HIV infection.
由于巨噬细胞在人类免疫缺陷病毒（HIV）所致疾病的发病机制中具有重要作用，我们研究了多种抗HIV药物对急性或慢性感染该病毒的人原代巨噬细胞的疗效。急性感染巨噬细胞的实验结果表明，双脱氧核苷（齐多夫定、去羟肌苷和双脱氧胞苷）、α-干扰素和γ-干扰素、错配双链RNA、Tat抑制剂、硫代磷酸酯反义核酸以及HIV蛋白酶抑制剂，在浓度远低于对细胞有毒性的浓度时，均能显著抑制病毒复制。然而，在原病毒DNA已整合的巨噬细胞（慢性感染巨噬细胞）中，只有三种HIV蛋白酶抑制剂在浓度比急性感染巨噬细胞中有效浓度高100倍或更高时，才会诱导显著的病毒抑制作用。用巨噬细胞集落刺激因子处理巨噬细胞并不影响蛋白酶抑制剂的抗HIV疗效。这些结果表明，对巨噬细胞有活性的治疗策略，包括HIV蛋白酶抑制剂，在HIV感染患者中值得探索。
