Collman R, Godfrey B, Cutilli J, Rhodes A, Hassan N F, Sweet R, Douglas S D, Friedman H, Nathanson N, Gonzalez-Scarano F
Department of Medicine, University of Pennsylvania Medical Center, Philadelphia.
J Virol. 1990 Sep;64(9):4468-76. doi: 10.1128/JVI.64.9.4468-4476.1990.
To characterize the role of CD4 in human immunodeficiency virus type 1 (HIV-1) infection of macrophages, we examined the expression of CD4 by primary human monocyte-derived macrophages and studied the effect of recombinant soluble CD4 and anti-CD4 monoclonal antibodies on HIV-1 infection of these cells. Immunofluorescence and Western blot (immunoblot) studies demonstrated that both monocytes and macrophages display low levels of surface CD4, which is identical in mobility to CD4 in lymphocytes. Recombinant soluble CD4 and the anti-CD4 monoclonal antibody Leu3a blocked infection of macrophages by three different macrophage-tropic HIV isolates, and the cytopathic effects of HIV-1 infection were similarly prevented. Dose-response experiments using a prototype isolate which replicates in both macrophages and T lymphocytes showed that recombinant soluble CD4 inhibited infection of macrophages more efficiently than in lymphocytes. These results indicate that CD4 is the dominant entry pathway for HIV-1 infection of macrophages. In addition, recombinant soluble CD4 effectively blocks HIV-1 infection by a variety of macrophage-tropic strains and thus has the potential for therapeutic use in macrophage-dependent pathogenesis in HIV disease.
为了描述CD4在1型人类免疫缺陷病毒（HIV-1）感染巨噬细胞中的作用，我们检测了原代人单核细胞衍生巨噬细胞中CD4的表达，并研究了重组可溶性CD4和抗CD4单克隆抗体对这些细胞HIV-1感染的影响。免疫荧光和蛋白质免疫印迹研究表明，单核细胞和巨噬细胞表面的CD4水平均较低，其迁移率与淋巴细胞中的CD4相同。重组可溶性CD4和抗CD4单克隆抗体Leu3a可阻断三种不同巨噬细胞嗜性HIV分离株对巨噬细胞的感染，并且同样可预防HIV-1感染的细胞病变效应。使用一种在巨噬细胞和T淋巴细胞中均能复制的原型分离株进行的剂量反应实验表明，重组可溶性CD4抑制巨噬细胞感染的效率高于淋巴细胞。这些结果表明，CD4是HIV-1感染巨噬细胞的主要进入途径。此外，重组可溶性CD4可有效阻断多种巨噬细胞嗜性毒株的HIV-1感染，因此在HIV疾病中巨噬细胞依赖性发病机制的治疗中具有潜在应用价值。
