Collman R G, Yi Y
Pulmonary and Critical Care Division, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-6060, USA. collmanr@mail. med.upenn.edu
J Infect Dis. 1999 May;179 Suppl 3:S422-6. doi: 10.1086/314797.
Macrophages are permissive for macrophage-tropic (M-tropic) human immunodeficiency virus type 1 (HIV-1) isolates that use CCR5 for entry but are resistant to CXCR-4-dependent T cell-tropic prototype strains. M-tropic variants are critical for HIV-1 transmission, and persons who are homozygous for an inactivating mutation of CCR5 are resistant to HIV-1 in vivo. In vitro, their macrophages and lymphocytes are resistant to M-tropic strains that depend on CCR5. It is shown that CCR5-deficient macrophages are permissive for a dual-tropic isolate, 89.6, that uses CCR5, CXCR-4, and other cofactors. Entry by 89.6 into CCR5-deficient macrophages was blocked by the CXCR-4 ligand SDF and by an anti-CXCR-4 antibody. Immunoflorescence staining and reverse transcription PCR confirmed macrophage CXCR-4 expression. Thus, CXCR-4 on macrophages mediates entry of certain dual-tropic but not T cell-tropic isolates. Therefore, HIV-1 strains differ in how they utilize chemokine receptors as cofactors for entry, and the ability of a chemokine receptor to facilitate entry depends on the cell in which it is expressed.
巨噬细胞对利用CCR5进入细胞的嗜巨噬细胞型1型人类免疫缺陷病毒（HIV-1）分离株敏感，但对依赖CXCR-4的嗜T细胞型原型毒株具有抗性。嗜巨噬细胞型变体对HIV-1传播至关重要，CCR5基因发生失活突变的纯合子个体在体内对HIV-1具有抗性。在体外，他们的巨噬细胞和淋巴细胞对依赖CCR5的嗜巨噬细胞型毒株具有抗性。研究表明，缺乏CCR5的巨噬细胞对一种双嗜性分离株89.6敏感，该分离株利用CCR5、CXCR-4和其他辅助因子。CXCR-4配体SDF和抗CXCR-4抗体可阻断89.6进入缺乏CCR5的巨噬细胞。免疫荧光染色和逆转录PCR证实了巨噬细胞CXCR-4的表达。因此，巨噬细胞上的CXCR-4介导某些双嗜性而非嗜T细胞型分离株的进入。因此，HIV-1毒株在利用趋化因子受体作为进入细胞的辅助因子的方式上存在差异，趋化因子受体促进进入的能力取决于其表达的细胞。
