Matsuda S, Akagawa K, Honda M, Yokota Y, Takebe Y, Takemori T
AIDS Research Center, National Institute of Health, Tokyo, Japan.
AIDS Res Hum Retroviruses. 1995 Sep;11(9):1031-8. doi: 10.1089/aid.1995.11.1031.
Susceptibility to HIV infection was examined in macrophages differentiated from human monocytes by macrophage colony-stimulating factor (M-CSF) or granulocyte/macrophage colony-stimulating factor (GM-CSF). The replication of macrophage-tropic human immunodeficiency virus type-1 (HIV-1), which was determined by reverse transcriptase (RT) activity, was significantly suppressed in macrophages induced by GM-CSF (GM-type macrophages) but not in those induced by M-CSF (M-type macrophages). Multinucleated giant cells were formed only in M-type macrophages after HIV infection. However, the expression of CD4 molecules on the surface of both types of macrophages was similar and the proviral DNA was detectable in cell lysates of both macrophages, although the amount of proviral DNA in M-type macrophages was higher than that in GM-type macrophages. Many steps have been defined in HIV infection and replication, such as adsorption of HIV to the cell surface, internalization of the viral core into the cytoplasm, uncoating of viral RNA, reverse transcription and integration of proviral DNA into cellular DNA, transcription and translation of proviral DNA, assembly of viral components, and budding of virus particles. Our findings suggested that the suppression of HIV-1 replication in macrophages induced by GM-CSF is mainly due to a disturbance at certain steps of replication after synthesis of the proviral DNA. Thus, the suppression of HIV replication in GM-type macrophages may provide a model of the latency of HIV infection in vivo.
通过巨噬细胞集落刺激因子（M-CSF）或粒细胞/巨噬细胞集落刺激因子（GM-CSF）从人单核细胞分化而来的巨噬细胞中检测了对HIV感染的易感性。通过逆转录酶（RT）活性测定的嗜巨噬细胞性1型人类免疫缺陷病毒（HIV-1）的复制在GM-CSF诱导的巨噬细胞（GM型巨噬细胞）中受到显著抑制，但在M-CSF诱导的巨噬细胞（M型巨噬细胞）中未受抑制。HIV感染后仅在M型巨噬细胞中形成多核巨细胞。然而，两种类型巨噬细胞表面CD4分子的表达相似，并且在两种巨噬细胞的细胞裂解物中均可检测到前病毒DNA，尽管M型巨噬细胞中的前病毒DNA量高于GM型巨噬细胞。HIV感染和复制过程已明确了许多步骤，如HIV吸附到细胞表面、病毒核心内化到细胞质、病毒RNA脱壳、逆转录以及前病毒DNA整合到细胞DNA中、前病毒DNA转录和翻译、病毒成分组装以及病毒颗粒出芽。我们的研究结果表明，GM-CSF诱导的巨噬细胞中HIV-1复制的抑制主要是由于前病毒DNA合成后复制的某些步骤受到干扰。因此，GM型巨噬细胞中HIV复制的抑制可能提供了体内HIV感染潜伏期的模型。
