双脱氧核苷在培养的人巨噬细胞中无法抑制人类免疫缺陷病毒复制。
Failure of dideoxynucleosides to inhibit human immunodeficiency virus replication in cultured human macrophages.
作者信息
Richman D D, Kornbluth R S, Carson D A
机构信息
Department of Pathology, University of California, San Diego 92161.
出版信息
J Exp Med. 1987 Oct 1;166(4):1144-9. doi: 10.1084/jem.166.4.1144.
Abstract
Primary human monocyte-derived macrophages (MDM) were shown to have diminished deoxynucleoside kinase activities compared to T lymphoblasts, and a reduced ability to phosphorylate dideoxynucleosides with anti-human immunodeficiency virus (HIV) activity. These drugs, azidothymidine (AZT), dideoxycytidine (ddC), and dideoxyadenosine (ddA), which are potent anti-HIV agents in CD4 lymphocytes, did not inhibit HIV replication in MDM, even at concentrations of 100 microM. This drug concentration of AZT is approximately 100-fold higher than the levels attained in the serum of treated patients and the levels required to inhibit HIV replication in lymphocytes. These observations may explain the failure of AZT therapy to clear viremia, consistent with the presence of a drug-resistant reservoir of infected cells in vivo. New therapeutic approaches to inhibit the replication of HIV in MDM may be needed.
摘要
与T淋巴母细胞相比，原代人单核细胞衍生的巨噬细胞（MDM）显示出脱氧核苷激酶活性降低，以及磷酸化具有抗人免疫缺陷病毒（HIV）活性的双脱氧核苷的能力降低。这些药物，叠氮胸苷（AZT）、双脱氧胞苷（ddC）和双脱氧腺苷（ddA），在CD4淋巴细胞中是有效的抗HIV药物，但即使在100微摩尔的浓度下，也不能抑制MDM中的HIV复制。AZT的这种药物浓度比治疗患者血清中达到的水平以及抑制淋巴细胞中HIV复制所需的水平高约100倍。这些观察结果可能解释了AZT治疗未能清除病毒血症的原因，这与体内存在耐药性感染细胞库一致。可能需要新的治疗方法来抑制MDM中HIV的复制。
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